WorldWideScience

Sample records for class ii antigen-presenting

  1. The systems biology of MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra

    2012-01-01

    Major histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC). They present peptides derived from endocytosed material to T helper lymphocytes. Consequently, MHC class

  2. MHC class II antigen presentation by B cells in health and disease

    NARCIS (Netherlands)

    Souwer, Yuri

    2009-01-01

    MHC class II antigen presentation by B cells is important to activate CD4+ T cells that stimulate the B cell to produce antibodies. Besides this, disruption of MHC class II antigen presentation could play a role in immune escape by tumor cells. This thesis describes MHC class II antigen presentation

  3. Targeting the MHC Class II antigen presentation pathway in cancer immunotherapy.

    Science.gov (United States)

    Thibodeau, Jacques; Bourgeois-Daigneault, Marie-Claude; Lapointe, Réjean

    2012-09-01

    The success of immunotherapy relies on the participation of all arms of the immune system and the role of CD4+ T lymphocytes in preventing tumor growth is now well established. Understanding how tumors evade immune responses holds the key to the development of cancer immunotherapies. In this review, we discuss how MHC Class II expression varies in cancer cells and how this influences antitumor immune responses. We also discuss the means that are currently available for harnessing the MHC Class II antigen presentation pathway for the development of efficient vaccines to activate the immune system against cancer.

  4. Hepatitis B virus-like particles access major histocompatibility class I and II antigen presentation pathways in primary dendritic cells.

    Science.gov (United States)

    Moffat, Jessica M; Cheong, Wan-Shoo; Villadangos, José A; Mintern, Justine D; Netter, Hans J

    2013-04-26

    Virus-like particles (VLPs) represent high density displays of viral proteins that efficiently trigger immunity. VLPs composed of the small hepatitis B virus envelope protein (HBsAgS) are useful vaccine platforms that induce humoral and cellular immune responses. Notably, however, some studies suggest HBsAgS VLPs impair dendritic cell (DC) function. Here we investigated HBsAgS VLP interaction with DC subsets and antigen access to major histocompatibility complex (MHC) class I and II antigen presentation pathways in primary DCs. HBsAgS VLPs impaired plasmacytoid DC (pDC) interferon alpha (IFNα) production in response to CpG in vitro, but did not alter conventional DC (cDC) or pDC phenotype when administered in vivo. To assess cellular immune responses, HBsAgS VLPs were generated containing the ovalbumin (OVA) model epitopes OVA(257-264) and OVA(323-339) to access MHCI and MHCII antigen presentation pathways, respectively; both in vitro and following immunisation in vivo. HBsAgS VLP-OVA(257-264) elicited CTL responses in vivo that were not enhanced by inclusion of an additional MHCII helper epitope. HBsAgS VLP-OVA(257-264) administered in vivo was cross-presented by CD8(+) DCs, but not CD8(-) DCs. Therefore, HBsAgS VLPs can deliver antigen to both MHCI and MHCII antigen presentation pathways in primary DCs and promote cytotoxic and helper T cell priming despite their suppressive effect on pDCs.

  5. Viral immune evasion: Lessons in MHC class I antigen presentation.

    Science.gov (United States)

    van de Weijer, Michael L; Luteijn, Rutger D; Wiertz, Emmanuel J H J

    2015-03-01

    The MHC class I antigen presentation pathway enables cells infected with intracellular pathogens to signal the presence of the invader to the immune system. Cytotoxic T lymphocytes are able to eliminate the infected cells through recognition of pathogen-derived peptides presented by MHC class I molecules at the cell surface. In the course of evolution, many viruses have acquired inhibitors that target essential stages of the MHC class I antigen presentation pathway. Studies on these immune evasion proteins reveal fascinating strategies used by viruses to elude the immune system. Viral immunoevasins also constitute great research tools that facilitate functional studies on the MHC class I antigen presentation pathway, allowing the investigation of less well understood routes, such as TAP-independent antigen presentation and cross-presentation of exogenous proteins. Viral immunoevasins have also helped to unravel more general cellular processes. For instance, basic principles of ER-associated protein degradation via the ubiquitin-proteasome pathway have been resolved using virus-induced degradation of MHC class I as a model. This review highlights how viral immunoevasins have increased our understanding of MHC class I-restricted antigen presentation.

  6. Induction of antigen-presenting capacity in tumor cells upon infection with non-replicating recombinant vaccinia virus encoding murine MHC class II and costimulatory molecules.

    Science.gov (United States)

    Marti, W R; Oertli, D; Meko, J B; Norton, J A; Tsung, K

    1997-01-15

    The possibility of inducing antigen-presenting capacity in cells normally lacking such capacity, currently represents a major goal in vaccine research. To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule. To minimize the cytopathic effect and to improve safety, in view of possible in vivo applications, we made this rVV replication incompetent by Psoralen and long wave UV treatment. Tumor cells infected with rVV encoding I-Ak alone, pulsed with hen egg white lysozyme peptide (HEL46-61), induced IL-2 secretion by an antigen-specific T hybridoma. Tumor cells infected with the rVV encoding mB7-1 provided costimulation for activating resting CD4+ T cells in the presence of ConA. Tumor cells infected with the rVV encoding I-Ak and mB7-1, and pulsed with chicken ovotransferrin peptide (conalbumin133-145), induced a significantly higher response in a specific Th2 cell clone (D10.G4.1) as compared to cells infected with rVV encoding I-Ak molecules only. Thus, this replication incompetent rVV represents a safe, multiple gene, vector system able to confer in one single infection step effective APC capacity to non-professional APCs.

  7. MHC Class I Antigen Presentation- Recently Trimmed and Well Presented

    Institute of Scientific and Technical Information of China (English)

    BarryFlutter; BinGao

    2004-01-01

    Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response. Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex. MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells. The cells presenting non-self peptides are cleared by CD8 positive T cells. In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated. Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer. Cellular & Molecular Immunology. 2004;1(1):22-30.

  8. MHC ClassAntigen Presentation- Recently Trimmed and Well Presented

    Institute of Scientific and Technical Information of China (English)

    Barry Flutter; Bin Gao

    2004-01-01

    Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class Ⅰ molecules is the key to the cellular immune response. Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class Ⅰ molecules assisted by several chaperone proteins to form trimeric complex. MHC class Ⅰ complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells. The cells presenting non-self peptides are cleared by CD8 positive T cells. In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class Ⅰ expression must be carefully regulated. Many of the cellular components involved in antigen processing and class Ⅰ presentation are known and their various functions are now becoming clearer. Cellular & Molecular Immunology. 2004;1(1):22-30.

  9. CD40-induced aggregation of MHC class II and CD80 on the cell surface leads to an early enhancement in antigen presentation.

    Science.gov (United States)

    Clatza, Abigail; Bonifaz, Laura C; Vignali, Dario A A; Moreno, José

    2003-12-15

    Ligation of CD40 on B cells increases their ability to present Ag and to activate MHC class II (MHC-II)-restricted T cells. How this occurs is not entirely clear. In this study we demonstrate that CD40 ligation on Ag-presenting B cells (APC) for a short period between 30 min and 3 h has a rapid, augmenting effect on the ability of a B cell line and normal B cells to activate T cells. This is not due to alterations in Ag processing or to an increase in surface expression of CD80, CD86, ICAM-1, or MHC-II. This effect is particularly evident with naive, resting T lymphocytes and appears to be more pronounced under limiting Ag concentrations. Shortly after CD40 ligation on a B cell line, MHC-II and CD80 progressively accumulated in cholesterol-enriched microdomains on the cell surface, which correlated with an initial enhancement in their Ag presentation ability. Moreover, CD40 ligation induced a second, late, more sustained enhancement of Ag presentation, which correlates with a significant increase in CD80 expression by APC. Thus, CD40 signaling enhances the efficiency with which APC activate T cells by at least two related, but distinct, mechanisms: an early stage characterized by aggregation of MHC-II and CD80 clusters, and a late stage in which a significant increase in CD80 expression is observed. These results raise the possibility that one important role of CD40 is to contribute to the formation of the immunological synapse on the APC side.

  10. Ultraviolet B-exposed major histocompatibility complex class II positive keratinocytes and antigen-presenting cells demonstrate a differential capacity to activate T cells in the presence of staphylococcal superantigens

    Energy Technology Data Exchange (ETDEWEB)

    Skov, L.; Baadsgaard, O. [Gentofte Hospital, Copenhagen (Denmark). Dept. of Dermatology

    1996-05-01

    In this study we tested the capacity of ultraviolet B (UVB)-irradiated major histocompatability complex (MHC) class II{sup +} keratinocytes, monocytes and dendritic cells to activate T cells in the presence of Staphylococcus enterotoxin B. We demonstrated that UVB irradiation of MHC class II{sup +} keratinocytes does not change their capacity to activate T cells in the presence of Staphylococcus enterotoxin B. In contrast, UVB irradiation of antigen-presenting cells decreases their capacity to activate T cells. The differential capacity to activate T cells after UVB irradiation was not due to factors released from UVB-irradiated cells. The interferon-{gamma} induced upregulation of HLA-DR and intercellular adhesion molecule-1 on keratinocytes does not seem to be the only explanation, since UVB irradiation decreased the accessory cell function of interferon-{gamma} pretreated monocytes. Differential requirements for and UVB regulation of costimulatory molecules may be involved, since blocking of the B7/CD28 pathway affects the capacity of dendritic cells but not keratinocytes to activate T cells in the presence of Staphylococcus enterotoxin B. Thus, MHC class II{sup +} keratinocytes in the presence of superantigens released from staphylococci may activate T cells and maintain inflammation despite UVB treatment. (Author).

  11. NLRC5 regulates MHC classantigen presentation in host defense against intracellular pathogens

    Institute of Scientific and Technical Information of China (English)

    Yikun Yao; Yalong Wang; Fuxiang Chen; Yin Huang; Shu Zhu; Qibin Leng; Hongyan Wang; Yufang Shi; Youcun Qian

    2012-01-01

    NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection.NLRC5,the largest member of the NLR family,has recently attracted much attention.However,in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways.The in vivo function of NLRC5 remains unknown.Here,we report that NLRC5 is a critical regulator of host defense against intraeellular pathogens in vivo.NLRC5 was specifically required for the expression of genes involved in MHC classantigen presentation.NLRC5-deficient mice showed a profound defect in the expression of MHC class Ⅰ genes and a concomitant failure to activate L.monocytogenes-specific CD8+ T cell responses,including activation,proliferation and cytotoxicity,and the mutant mice were more susceptible to the pathogen infection.NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice.However,NLRC5 was dispensable for pathogen-induced expression of NF-KB-dependent pro-inflammatory genes as well as type I interferon genes.Thus,NLRC5 critically regulates MHC classantigen presentation to control intracellular pathogen infection.

  12. Ethanol Metabolism Alters Major Histocompatibility Complex Class I-Restricted Antigen Presentation In Liver Cells

    Science.gov (United States)

    Osna, Natalia A.; White, Ronda L.; Thiele, Geoffrey M.; Donohue, Terrence M.

    2009-01-01

    The proteasome is a major enzyme that cleaves proteins for antigen presentation. Cleaved peptides traffic to the cell surface, where they are presented in the context of MHC class I. Recognition of these complexes by cytotoxic T lymphocytes is crucial for elimination of cells bearing “non-self” proteins. Our previous studies revealed that ethanol suppresses proteasome function in ethanol-metabolizing liver cells. We hypothesized that proteasome suppression reduces the hydrolysis of antigenic peptides, thereby decreasing the presentation of the peptide-MHC class I-complexes on the cell surface. To test this, we used the mouse hepatocyte cell line (CYP2E1/ADH-transfected HepB5 cells) or primary mouse hepatocytes, both derived from livers of C57Bl/6 mice, which present the ovalbumin peptide, SIINFEKL, complexed with H2Kb. To induce H2Kb expression, HepB5 cells were treated with interferon gamma (IFNγ) and then exposed to ethanol. In these cells, ethanol metabolism decreased not only proteasome activity, but also hydrolysis of the C-extended peptide, SIINFEKL-TE and the presentation of SIINFEKL-H2Kb complexes measured after the delivery of SIINFEKL-TE to cytoplasm. The suppressive effects of ethanol were, in part, attributed to ethanol-elicited impairment of IFNγ signaling. However, in primary hepatocytes, even in the absence of IFNγ, we observed a similar decline in proteasome activity and antigen presentation after ethanol exposure. We conclude that proteasome function is directly suppressed by ethanol metabolism and indirectly, by preventing the activating effects of IFNγ. Ethanol-elicited reduction in proteasome activity contributes to the suppression of SIINFEKL-H2Kb presentation on the surface of liver cells. Immune response to viral antigens plays a crucial role in the pathogenesis of hepatitis C or B viral infections (HCV and HBV, respectively). Professional antigen-presenting cells (dendritic cells and macrophages) are responsible for priming the

  13. EpsinR, a target for pyrenocine B, role in endogenous MHC-II-restricted antigen presentation.

    Science.gov (United States)

    Shishido, Tatsuya; Hachisuka, Masami; Ryuzaki, Kai; Miura, Yuko; Tanabe, Atsushi; Tamura, Yasuaki; Kusayanagi, Tomoe; Takeuchi, Toshifumi; Kamisuki, Shinji; Sugawara, Fumio; Sahara, Hiroeki

    2014-11-01

    While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen.

  14. Organizing MHC Class II Presentation

    Directory of Open Access Journals (Sweden)

    David R Fooksman

    2014-04-01

    Full Text Available Major histocompatibility complex (MHC class II molecules are ligands for CD4+ T cells and are critical for initiating the adaptive immune response. This review is focused on what is currently known about MHC class II organization at the plasma membrane of antigen presenting cells and how this affects antigen presentation to T cells. The organization and diffusion of class II molecules have been measured by a variety of biochemical and microscopic techniques. Membrane lipids and other proteins have been implicated in MHC class II organization and function. However, when compared with the organization of MHC class I or TCR complexes, much less is known about MHC class II. Since clustering of T cell receptors occurs during activation, the organization of MHC molecules prior to recognition and during synapse formation may be critical for antigen presentation.

  15. P2X7 Receptor Activation Impairs Exogenous MHC Class I Oligopeptides Presentation in Antigen Presenting Cells

    OpenAIRE

    Alberto Baroja-Mazo; Maria Barberà-Cremades; Pablo Pelegrín

    2013-01-01

    Major histocompatibility complex class I (MHC I) on antigen presenting cells (APCs) is a potent molecule to activate CD8(+) T cells and initiate immunity. P2X7 receptors (P2X7Rs) are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5'-triphosphate (ATP). P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the a...

  16. P2X7 receptor activation impairs exogenous MHC class I oligopeptides presentation in antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Alberto Baroja-Mazo

    Full Text Available Major histocompatibility complex class I (MHC I on antigen presenting cells (APCs is a potent molecule to activate CD8(+ T cells and initiate immunity. P2X7 receptors (P2X7Rs are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5'-triphosphate (ATP. P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the amount of MHC I at the plasma membrane. Specific antagonism or genetic ablation of P2X7R inhibited the effects of ATP on levels of cellular MHC I. Furthermore, P2X7R stimulation was able to inhibit activation of CD8(+ T cells via specific MHC I-oligopeptide complexes. Our study suggests that P2X7R activation on APCs is a novel inhibitor of adaptive CD8(+ T cell immunity.

  17. Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.

    Science.gov (United States)

    Vlková, Veronika; Štěpánek, Ivan; Hrušková, Veronika; Šenigl, Filip; Mayerová, Veronika; Šrámek, Martin; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Hejhal, Tomáš; Dérian, Nicolas; Klatzmann, David; Six, Adrien; Reiniš, Milan

    2014-08-30

    Downregulation of MHC class I expression on tumour cells, a common mechanism by which tumour cells can escape from specific immune responses, can be associated with coordinated silencing of antigen-presenting machinery genes. The expression of these genes can be restored by IFNγ. In this study we documented association of DNA demethylation of selected antigen-presenting machinery genes located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFNγ treatment with MHC class I upregulation on tumour cells in several MHC class I-deficient murine tumour cell lines (TC-1/A9, TRAMP-C2, MK16 and MC15). Our data also documented higher methylation levels in these genes in TC-1/A9 cells, as compared to their parental MHC class I-positive TC-1 cells. IFNγ-mediated DNA demethylation was relatively fast in comparison with demethylation induced by DNA methyltransferase inhibitor 5-azacytidine, and associated with increased histone H3 acetylation in the promoter regions of APM genes. Comparative transcriptome analysis in distinct MHC class I-deficient cell lines upon their treatment with either IFNγ or epigenetic agents revealed that a set of genes, significantly enriched for the antigen presentation pathway, was regulated in the same manner. Our data demonstrate that IFNγ acts as an epigenetic modifier when upregulating the expression of antigen-presenting machinery genes.

  18. Pseudomonas aeruginosa Cif protein enhances the ubiquitination and proteasomal degradation of the transporter associated with antigen processing (TAP) and reduces major histocompatibility complex (MHC) class I antigen presentation.

    Science.gov (United States)

    Bomberger, Jennifer M; Ely, Kenneth H; Bangia, Naveen; Ye, Siying; Green, Kathy A; Green, William R; Enelow, Richard I; Stanton, Bruce A

    2014-01-03

    Cif (PA2934), a bacterial virulence factor secreted in outer membrane vesicles by Pseudomonas aeruginosa, increases the ubiquitination and lysosomal degradation of some, but not all, plasma membrane ATP-binding cassette transporters (ABC), including the cystic fibrosis transmembrane conductance regulator and P-glycoprotein. The goal of this study was to determine whether Cif enhances the ubiquitination and degradation of the transporter associated with antigen processing (TAP1 and TAP2), members of the ABC transporter family that play an essential role in antigen presentation and intracellular pathogen clearance. Cif selectively increased the amount of ubiquitinated TAP1 and increased its degradation in the proteasome of human airway epithelial cells. This effect of Cif was mediated by reducing USP10 deubiquitinating activity, resulting in increased polyubiquitination and proteasomal degradation of TAP1. The reduction in TAP1 abundance decreased peptide antigen translocation into the endoplasmic reticulum, an effect that resulted in reduced antigen available to MHC class I molecules for presentation at the plasma membrane of airway epithelial cells and recognition by CD8(+) T cells. Cif is the first bacterial factor identified that inhibits TAP function and MHC class I antigen presentation.

  19. Antigen presentation by MHC-dressed cells

    Directory of Open Access Journals (Sweden)

    Masafumi eNakayama

    2015-01-01

    Full Text Available Professional antigen presenting cells (APCs such as conventional dendritic cells (DCs process protein antigens to MHC-bound peptides and then present the peptide-MHC complexes to T cells. In addition to this canonical antigen presentation pathway, recent studies have revealed that DCs and non-APCs can acquire MHC class I (MHCI and/or MHC class II (MHCII from neighboring cells through a process of cell-cell contact-dependent membrane transfer called trogocytosis. These MHC-dressed cells subsequently activate or regulate T cells via the preformed antigen peptide-MHC complexes without requiring any further processing. In addition to trogocytosis, intercellular transfer of MHCI and MHCII can be mediated by secretion of membrane vesicles such as exosomes from APCs, generating MHC-dressed cells. This review focuses on the physiological role of antigen presentation by MHCI- or MHCII-dressed cells, and also discusses differences and similarities between trogocytosis and exosome-mediated transfer of MHC.

  20. Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes.

    Science.gov (United States)

    Van Overtvelt, Laurence; Andrieu, Muriel; Verhasselt, Valérie; Connan, Francine; Choppin, Jeannine; Vercruysse, Vincent; Goldman, Michel; Hosmalin, Anne; Vray, Bernard

    2002-10-01

    Trypanosoma cruzi, the etiological agent of Chagas' disease, may persist for many years in its mammalian host. This suggests escape from the immune response and particularly a suboptimal CD8(+) T cell response, since these cells are involved in infection control. In this report, we show that T. cruzi inhibits the lipopolysaccharide (LPS)-induced up-regulation of MHC class I molecules at the surface of human dendritic cells (DC). To further investigate the functional consequences of this inhibition, a trypomastigote surface antigen-derived peptide (TSA-1(514-522) peptide) was selected for its stable binding to HLA-A*0201 molecules and used to generate a primary T. cruzi-specific human CD8(+) T cell line in vitro. We observed that DC infected with T. cruzi or treated with T. cruzi-conditioned medium (TCM) had a weaker capacity to present this peptide to the specific CD8(+) T cell line as shown in an IFN-gamma ELISPOT assay. Interestingly, T. cruzi or TCM also reduced the antigen presentation capacity of DC to CD8(+) T cell lines specific for the influenza virus M(58-66) or HIV RT(476-484) epitopes. This dysfunction appears to be linked essentially to reduced MHC class I molecule expression since the stimulation of the RT(476-484) peptide-specific CD8(+) T cell line was shown to depend mainly on the MHC class I-TCR interaction and not on the co-stimulatory signals which, however, were also inhibited by T. cruzi. This impairment of DC function may represent a novel mechanism reducing in vivo the host's ability to combat efficiently T. cruzi infection.

  1. MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation

    DEFF Research Database (Denmark)

    Rosloniec, E F; Vitez, L J; Buus, S

    1990-01-01

    found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k-3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323......-339) immunodominant peptide to the I-Ad-restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3...

  2. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8(+) T Cells.

    Science.gov (United States)

    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-02

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8(+) cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4(+) and CD8(+) T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4(+) and CD8(+) T cells. Furthermore, lymphoid CD8(+) T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8(+) T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8(+) T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  3. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

    Science.gov (United States)

    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-01

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  4. Class II Microcins

    Science.gov (United States)

    Vassiliadis, Gaëlle; Destoumieux-Garzón, Delphine; Peduzzi, Jean

    Class II microcins are 4.9- to 8.9-kDa polypeptides produced by and active against enterobacteria. They are classified into two subfamilies according to their structure and their gene cluster arrangement. While class IIa microcins undergo no posttranslational modification, class IIb microcins show a conserved C-terminal sequence that carries a salmochelin-like siderophore motif as a posttranslational modification. Aside from this C-terminal end, which is the signature of class IIb microcins, some sequence similarities can be observed within and between class II subclasses, suggesting the existence of common ancestors. Their mechanisms of action are still under investigation, but several class II microcins use inner membrane proteins as cellular targets, and some of them are membrane-active. Like group B colicins, many, if not all, class II microcins are TonB- and energy-dependent and use catecholate siderophore receptors for recognition/­translocation across the outer membrane. In that context, class IIb microcins are considered to have developed molecular mimicry to increase their affinity for their outer membrane receptors through their salmochelin-like posttranslational modification.

  5. Properties of glycolipid-enriched membrane rafts in antigen presentation.

    Science.gov (United States)

    Rodgers, William; Smith, Kenneth

    2005-01-01

    Presentation of antigen to T cells represents one of the central events in the engagement of the immune system toward the defense of the host against pathogens. Accordingly, understanding the mechanisms by which antigen presentation occurs is critical toward our understanding the properties of host defense against foreign antigen, as well as insight into other features of the immune system, such as autoimmune disease. The entire antigen-presentation event is complex, and many features of it remain poorly understood. However, recent studies have provided evidence showing that glycolipid-enriched membrane rafts are important for efficient antigen presentation; the studies suggest that one such function of rafts is trafficking of antigen-MHC II complexes to the presentation site on the surface of the antigen-presenting cell. Here, we present a critical discussion of rafts and their proposed functions in antigen presentation. Emerging topics of rafts and antigen presentation that warrant further investigation are also highlighted.

  6. Role of metalloproteases in vaccinia virus epitope processing for transporter associated with antigen processing (TAP)-independent human leukocyte antigen (HLA)-B7 class I antigen presentation.

    Science.gov (United States)

    Lorente, Elena; García, Ruth; Mir, Carmen; Barriga, Alejandro; Lemonnier, François A; Ramos, Manuel; López, Daniel

    2012-03-23

    The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8(+) lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8(+) T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP-deficient individuals live normal life spans without any increased susceptibility to viral infections.

  7. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Science.gov (United States)

    Maj, Tomasz; Slawek, Anna

    2014-01-01

    Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs) derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA) were cocultured with CD4+ T cells derived from OT-II mice's (C57BL6/J-Tg(TcraTcrb)1100Mjb/J) spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU), activation of these cells (flow cytometry), cytokine profile (ELISA), and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear. PMID:24771983

  8. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

    Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

  9. Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47.

    Science.gov (United States)

    Saini, Neeraj K; Baena, Andres; Ng, Tony W; Venkataswamy, Manjunatha M; Kennedy, Steven C; Kunnath-Velayudhan, Shajo; Carreño, Leandro J; Xu, Jiayong; Chan, John; Larsen, Michelle H; Jacobs, William R; Porcelli, Steven A

    2016-08-15

    Suppression of major histocompatibility complex (MHC) class II antigen presentation is believed to be among the major mechanisms used by Mycobacterium tuberculosis to escape protective host immune responses. Through a genome-wide screen for the genetic loci of M. tuberculosis that inhibit MHC class II-restricted antigen presentation by mycobacteria-infected dendritic cells, we identified the PE_PGRS47 protein as one of the responsible factors. Targeted disruption of the PE_PGRS47 (Rv2741) gene led to attenuated growth of M. tuberculosis in vitro and in vivo, and a PE_PGRS47 mutant showed enhanced MHC class II-restricted antigen presentation during in vivo infection of mice. Analysis of the effects of deletion or over-expression of PE_PGRS47 implicated this protein in the inhibition of autophagy in infected host phagocytes. Our findings identify PE_PGRS47 as a functionally relevant, non-redundant bacterial factor in the modulation of innate and adaptive immunity by M. tuberculosis, suggesting strategies for improving antigen presentation and the generation of protective immunity during vaccination or infection.

  10. Immune control of tumors by antigen presentation improvement.

    Science.gov (United States)

    Remedi, María Mónica; Bonacci, Gustavo; Vides, Miguel Angel; Donadio, Ana Carolina

    2003-01-01

    Tumor cells cannot activate T lymphocytes, since they do not usually express major histocompatibility complex (MHC) class II molecules. Thus, tumor antigens can only be presented indirectly to T cells through professional antigen-presenting cells (APC). In our laboratory, we have treated a tumor cell line (Tu1-A) - derived from an induced rat mammary sarcoma - in order to increase the expression of MHC class I and class II molecules. In our tumor model, the transference of these induced cells into normal rats generated a tumor mass that exhibited a lower tumor growth rate and an earlier regression as compared to those observed in rats inoculated with wild-type Tu1-A cells. This earlier tumor regression was associated with the development of an antigen-specific immune response. 85-87% of the rats in both groups rejected the tumor and were alive at day 60 after tumor cell inoculation. However, in rats treated with wild-type cells the rejection was delayed and took place after tumor ulceration. Rats that had rejected tumors were rechallenged with wild-type cells in order to assay the presence of a long-lived antitumor immunity. All the animals were resistant to the second tumor challenge. We conclude that the development of a specific immune response could be achieved by the superexpression of MHC molecules on tumor cells or when tumor ulceration promotes APC to take up necrotic cells and tumor antigens are presented to T lymphocytes.

  11. In vivo requirement for Atg5 in antigen presentation by dendritic cells.

    Science.gov (United States)

    Lee, Heung Kyu; Mattei, Lisa M; Steinberg, Benjamin E; Alberts, Philipp; Lee, Yun Hee; Chervonsky, Alexander; Mizushima, Noboru; Grinstein, Sergio; Iwasaki, Akiko

    2010-02-26

    Autophagy is known to be important in presentation of cytosolic antigens on MHC class II (MHC II). However, the role of autophagic process in antigen presentation in vivo is unclear. Mice with dendritic cell (DC)-conditional deletion in Atg5, a key autophagy gene, showed impaired CD4(+) T cell priming after herpes simplex virus infection and succumbed to rapid disease. The most pronounced defect of Atg5(-/-) DCs was the processing and presentation of phagocytosed antigens containing Toll-like receptor stimuli for MHC class II. In contrast, cross-presentation of peptides on MHC I was intact in the absence of Atg5. Although induction of metabolic autophagy did not enhance MHC II presentation, autophagic machinery was required for optimal phagosome-to-lysosome fusion and subsequent processing of antigen for MHC II loading. Thus, our study revealed that DCs utilize autophagic machinery to optimally process and present extracellular microbial antigens for MHC II presentation.

  12. Direct Activation of Human Dendritic Cells by Particle-Bound but Not Soluble MHC Class II Ligand

    NARCIS (Netherlands)

    R.B. Baleeiro (Renato); K.H. Wiesmüller (Karl Heinz); L. Dähne (Lars); J. Lademann (Jürgen); J.A. Barbuto (José); P. Walden (Peter)

    2013-01-01

    textabstractDendritic cells (DCs) are key activators of cellular immune responses through their capacity to induce naïve T cells and sustained effector T cell responses. This capacity is a function of their superior efficiency of antigen presentation via MHC class I and class II molecules, and the e

  13. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

    NARCIS (Netherlands)

    Buschow, S.I.; Balkom, B.W.M. van; Aalberts, M.; Heck, A.J.R. van; Wauben, M.; Stoorvogel, W.

    2010-01-01

    Professional antigen-presenting cells secrete major histocompatibility complex class II (MHC II) carrying exosomes with unclear physiological function(s). Exosomes are first generated as the intraluminal vesicles (ILVs) of a specific type of multivesicular body, and are then secreted by fusion of th

  14. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Wei eXu

    2014-01-01

    Full Text Available The professional antigen presenting cells (APCs, including many subsets of dendritic cells and macrophages, not only mediate prompt but nonspecific response against microbes, but also bridge the antigen-specific adaptive immune response through antigen presentation. In the latter, typically activated B cells acquire cognate signals from T helper cells in the germinal center of lymphoid follicles to differentiate into plasma cells, which generate protective antibodies. Recent advances have revealed that many APC subsets provide not only signal 1 (the antigen, but also signal 2 to directly instruct the differentiation process of plasma cells in a T cell-independent manner. Herein, the different signals provided by these APC subsets to direct B cell proliferation, survival, class switching and terminal differentiation are discussed. We furthermore propose that the next generation of vaccines for boosting antibody response could be designed by targeting APCs.

  15. Human invariant chain isoform p35 restores thymic selection and antigen presentation in CD74-deficient mice.

    Science.gov (United States)

    Genève, Laetitia; Chemali, Magali; Desjardins, Michel; Labrecque, Nathalie; Thibodeau, Jacques

    2012-10-01

    The invariant chain (Ii) has pleiotropic functions and is a key factor in antigen presentation. Ii associates with major histocompatibility complex class II molecules in the endoplasmic reticulum (ER) and targets the complex in the endocytic pathway to allow antigenic peptide loading. The human Iip35 isoform includes a cytoplasmic extension containing a di-arginine motif causing ER retention. This minor isoform does not exist in mice and its function in humans has not been thoroughly investigated. We have recently generated transgenic mice expressing Iip35 and these were crossed with Ii-deficient mice to generate animals (Tgp35/mIiKO) expressing exclusively the human isoform. In these mice, we show that Iip35 is expressed in antigen presenting cells and is inducible by interferon gamma (IFN-γ). Despite the low constitutive expression of the protein and some minor differences in the Vβ repertoire of Tgp35/mIiKO mice, Iip35 restored thymic selection of CD4(+) T cells and of invariant natural killer T cells. In vitro functional assays using purified primary macrophages treated with IFN-γ showed that Iip35 allows presentation of an Ii-dependent ovalbumin T-cell epitope. Altogether, our results suggest that Iip35 is functional and does not require co-expression of other isoforms for antigen presentation.

  16. The perivascular phagocyte of the mouse pineal gland: An antigen-presenting cell

    DEFF Research Database (Denmark)

    Møller, Morten; Rath, Martin F; Klein, David C

    2006-01-01

    The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal...... gland of mice. Actively phagocytosing cells with a prominent lysosomal system were found in the pericapillary spaces of the mouse pineal gland following intravenous injection of horseradish peroxidase. The cells also exhibited strong acid phosphatase activity. Perivascular cells were immunopositive...... for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen-presenting properties are present in the mouse pineal gland....

  17. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  18. Cordyceps militaris Enhances MHC-restricted Antigen Presentation via the Induced Expression of MHC Molecules and Production of Cytokines

    Science.gov (United States)

    Shin, Seulmee; Park, Yoonhee; Kim, Seulah; Oh, Hee-Eun; Ko, Young-Wook; Han, Shinha; Lee, Seungjeong; Lee, Chong-Kil; Cho, Kyunghae

    2010-01-01

    Background Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). Methods Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. Results CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. Conclusion These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs. PMID:20844738

  19. Preferred SLA class I/class II haplotype combinations in German Landrace pigs.

    Science.gov (United States)

    Gimsa, Ulrike; Ho, Chak-Sum; Hammer, Sabine E

    2017-01-01

    Major histocompatibility complex (MHC) molecules are responsible for the antigen presentation to T lymphocytes. High recombination rates in the MHC genes, as observed in humans, are believed to serve the evolutionary goal to achieve a high genetic diversity, allowing for a broad and efficient immune response. In a cohort of 155 pedigreed German Landrace pigs (65 founders and 90 piglets), we found that MHC genes occur in particular class I and class II haplotype combinations. This phenomenon has not been described before, probably because most of the earlier MHC studies in pigs were not pedigree-based. After comparing our data with published genotypes of different European pig breeds and Asian pigs, we hypothesise that the combination of particular but different haplotypes in different geographical regions may have developed under the evolutionary pressure of regionally endemic pathogens. This proposed mechanism ensures an efficient immune response despite low recombination rates.

  20. Simvastatin inhibits interferon-γ-induced MHC class II up-regulation in cultured astrocytes

    Directory of Open Access Journals (Sweden)

    Glazenburg Lisa

    2006-07-01

    Full Text Available Abstract Based on their potent anti-inflammatory properties and a preliminary clinical trial, statins (HMG-CoA reductase inhibitors are being studied as possible candidates for multiple sclerosis (MS therapy. The pathogenesis of MS is unclear. One theory suggests that the development of autoimmune lesions in the central nervous system may be due to a failure of endogenous inhibitory control of MHC class II expression on astrocytes, allowing these cells to adapt an interferon (IFN-γ-induced antigen presenting phenotype. By using immunocytochemistry in cultured astrocytes derived from newborn Wistar rats we found that simvastatin at nanomolar concentrations inhibited, in a dose-response fashion, up to 70% of IFN-γ-induced MHC class II expression. This effect was reversed by the HMG-CoA reductase product mevalonate. Suppression of the antigen presenting function of astrocytes might contribute to the beneficial effects of statins in MS.

  1. The bovine class II major histocompatibility complex: Serological definition and further characterization of class II haplotypes.

    NARCIS (Netherlands)

    Nilsson, Ph.R.

    1994-01-01

    In this thesis an analysis of the major histocompatibility complex (MHC) class II in cattle is reported, with emphasis on the development of class II serology. First, the production of class II alloantisera, and the serological definition of bovine MHC class II polymorphism is described. Subsequentl

  2. Mechanistic understanding and significance of small peptides interaction with MHC class II molecules for therapeutic applications.

    Science.gov (United States)

    Afridi, Saifullah; Hoessli, Daniel C; Hameed, Muhammad Waqar

    2016-07-01

    Major histocompatibility complex (MHC) class II molecules are expressed by antigen-presenting cells and stimulate CD4(+) T cells, which initiate humoral immune responses. Over the past decade, interest has developed to therapeutically impact the peptides to be exposed to CD4(+) T cells. Structurally diverse small molecules have been discovered that act on the endogenous peptide exchanger HLA-DM by different mechanisms. Exogenously delivered peptides are highly susceptible to proteolytic cleavage in vivo; however, it is only when successfully incorporated into stable MHC II-peptide complexes that these peptides can induce an immune response. Many of the small molecules so far discovered have highlighted the molecular interactions mediating the formation of MHC II-peptide complexes. As potential drugs, these small molecules open new therapeutic approaches to modulate MHC II antigen presentation pathways and influence the quality and specificity of immune responses. This review briefly introduces how CD4(+) T cells recognize antigen when displayed by MHC class II molecules, as well as MHC class II-peptide-loading pathways, structural basis of peptide binding and stabilization of the peptide-MHC complexes. We discuss the concept of MHC-loading enhancers, how they could modulate immune responses and how these molecules have been identified. Finally, we suggest mechanisms whereby MHC-loading enhancers could act upon MHC class II molecules.

  3. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance.

    Science.gov (United States)

    Bonifaz, Laura; Bonnyay, David; Mahnke, Karsten; Rivera, Miguel; Nussenzweig, Michel C; Steinman, Ralph M

    2002-12-16

    To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of alphaDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with alphaDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic alphaCD40 antibody produced large amounts of interleukin 2 and interferon gamma, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.

  4. Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance

    Science.gov (United States)

    Bonifaz, Laura; Bonnyay, David; Mahnke, Karsten; Rivera, Miguel; Nussenzweig, Michel C.; Steinman, Ralph M.

    2002-01-01

    To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation. PMID:12486105

  5. MHC structure and function − antigen presentation. Part 2

    Science.gov (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells. PMID:25807243

  6. ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

    DEFF Research Database (Denmark)

    Faraco, Juliette; Lin, Ling; Kornum, Birgitte Rahbek;

    2013-01-01

    Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals...... with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell...... receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells...

  7. ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Juliette Faraco

    Full Text Available Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip. Three loci located outside the Human Leukocyte Antigen (HLA region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@, variants in two additional narcolepsy loci, Cathepsin H (CTSH and Tumor necrosis factor (ligand superfamily member 4 (TNFSF4, also called OX40L, attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

  8. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

    Science.gov (United States)

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

    2016-08-11

    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD.

  9. Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

    Science.gov (United States)

    Villarroel-Dorrego, Mariana; Speight, Paul M; Barrett, A William

    2005-01-01

    Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

  10. Early failure of Class II resin composite versus Class II amalgam restorations placed by dental students.

    Science.gov (United States)

    Overton, J D; Sullivan, Diane J

    2012-03-01

    Using the information from remake request slips in a dental school's predoctoral clinic, we examined the short-term survival of Class II resin composite restorations versus Class II dental amalgam restorations. In the student clinic, resin composite is used in approximately 58 percent of Class II restorations placed, and dental amalgam is used in the remaining 42 percent. In the period examined, Class II resin composite restorations were ten times more likely to be replaced at no cost to the patient than Class II dental amalgam restorations. A total of eighty-four resin composite restorations and six amalgam restorations were replaced due to an identified failure.

  11. The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ.

    Science.gov (United States)

    Chesney, J; Bacher, M; Bender, A; Bucala, R

    1997-06-10

    Recent studies have identified a novel population of blood-borne cells, termed fibrocytes, that have a distinct cell surface phenotype (collagen+/CD13(+)/CD34(+)/CD45(+)), rapidly enter sites of tissue injury, and synthesize connective tissue matrix molecules. We found by flow cytometry that purified human fibrocytes express each of the known surface components that are required for antigen presentation, including class II major histocompatability complex molecules (HLA-DP, -DQ, and -DR), the costimulatory molecules CD80 and CD86, and the adhesion molecules CD11a, CD54, and CD58. Human fibrocytes induced antigen-presenting cell-dependent T cell proliferation when cultured with specific antigen and this proliferative activity was significantly higher than that induced by monocytes and nearly as high as that induced by purified dendritic cells. Mouse fibrocytes also were found to express the surface components required for antigen presentation and to function as potent APCs in vitro. Mouse fibrocytes pulsed in vitro with the HIV-proteins p24 or gp120 and delivered to a site of cutaneous injury were found to migrate to proximal lymph nodes and to specifically prime naive T cells. These data suggest that fibrocytes play an early and important role in the initiation of antigen-specific immunity.

  12. Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules.

    Science.gov (United States)

    Grødeland, Gunnveig; Bogen, Bjarne

    2015-06-01

    There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.

  13. Structural Properties of MHC Class II Ligands, Implications for the Prediction of MHC Class II Epitopes

    DEFF Research Database (Denmark)

    Jørgensen, Kasper Winther; Buus, Søren; Nielsen, Morten

    2010-01-01

    properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure......Major Histocompatibility class II (MHC-II) molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule...... of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC...

  14. The Relationship between Class I and Class II Methanol Masers

    CERN Document Server

    Ellingsen, S P

    2005-01-01

    The Australia Telescope National Facility Mopra millimetre telescope has been used to search for 95.1-GHz class I methanol masers towards sixty-two 6.6-GHz class II methanol masers. A total of twenty-six 95.1-GHz masers were detected, eighteen of these being new discoveries. Combining the results of this search with observations reported in the literature, a near complete sample of sixty-six 6.6-GHz class II methanol masers has been searched in the 95.1-GHz transition, with detections towards 38 per cent (twenty-five detections ; not all of the sources studied in this paper qualify for the complete sample, and some of the sources in the sample were not observed in the present observations). There is no evidence of an anti-correlation between either the velocity range, or peak flux density of the class I and II transitions, contrary to suggestions from previous studies. The majority of class I methanol maser sources have a velocity range that partially overlaps with the class II maser transitions. The presence...

  15. Class II-associated invariant chain peptide down-modulation enhances the immunogenicity of myeloid leukemic blasts resulting in increased CD4(+) T-cell responses

    NARCIS (Netherlands)

    van Luijn, M.M.; Chamuleau, M.E.D.; Thompson, J.A.; Ostrand-Rosenberg, S.; Westers, T.M.; Souwer, Y.; Ossenkoppele, G.J.; Ham, S.M.; van de Loosdrecht, A.A.

    2010-01-01

    Background Disease recurrence in patients with acute myeloid leukemia may be partially explained by the escape of leukemic blasts from CD4(+) T-cell recognition. The current study investigates the role of aberrant HLA class II antigen presentation on leukemic blasts by determining both the clinical

  16. Hepatitis C virus and ethanol alter antigen presentation in liver cells

    Institute of Scientific and Technical Information of China (English)

    Natalia A Osna

    2009-01-01

    Alcoholic patients have a high incidence of hepatitis Cvirus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCVinduced inability of the immune system to recognizeinfected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) classⅠ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC classⅠand class Ⅱ in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance,preventing cell maturation and allostimulation capacity.The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC classⅠ-restricted antigen presentation.Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

  17. Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Jonathan Harton

    2016-03-01

    Full Text Available Major histocompatibility complex (MHC class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naïve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II α and β chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail mediates these “non-traditional” class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease.

  18. Set Theory Applied to the Mathematical Characterization of HLA Class II Binding Peptides

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez Velásquez, MD, esp.1

    2008-04-01

    Full Text Available Antigen presentation contains the molecularbasis for antigenic identification and immuneresponses. The set theory and experimental datawere used in order to develop an union core regionmathematic characterization through the definitionof 8 laws associated to HLA class II binding.The laws were applied to 4 promiscuous peptides,25 natural peptides sequences of core region: 13binding peptides and 12 no binding peptides; and19 synthetic peptides looking to differentiate peptides.Only one peptide was not rightly characterized.This methodology may be used to choose keypeptides in the development of vaccine.

  19. SPONGIOTIC DERMATITIS WITH A MIXED INFLAMMATORY INFILTRATE OF LYMPHOCYTES, ANTIGEN PRESENTING CELLS, IMMUNOGLOBULINS AND COMPLEMENT

    Directory of Open Access Journals (Sweden)

    Abreu Velez Ana Maria

    2011-04-01

    Full Text Available Background: The clinical and histological presentation of spongiotic dermatitis and its inflammatory infiltrates warrant further investigation. In this case documentation of a patient with cutaneous spongiotic reactivity, we aim to characterize antigen presenting cells, as well as the skin-specific cutaneous lymphocyte antigen population by multiple techniques. Case report: A 30 year old Caucasian female presented with a two week history of blistering and erosions around the vaginal, rectal and axillary areas. Material and Methods: We utilized hematoxylin and eosin histology, direct immunofluorescence, immunohistochemistry and confocal microscopy methods to evaluate the immune reaction patterns of the cutaneous inflammatory cells. Results: In the primary histologic areas of spongiotic dermatitis, a mixed population of B and T lymphocytes was seen. Ki-67 antigen proliferative index staining was accentuated in these areas, correlating with the presence of large numbers of epidermal and dermal antigen presenting cells. Among the antigen presenting cell population, we detected strong positivities with CD1a, Factor XIIIa, myeloid/hystoid antigen, S100, HAM-56, and CD68. Interestingly, immunoglobulins G, D and M and Complement factors C1q and C3 were also strongly expressed in antigen presenting cell areas, including positivity within the spongiotic epidermis and around dermal vessels. Conclusions: We document a heterogeneous population of B and T lymphocytes and the presence of multiple classes of antigen presenting cells, immunoglobulins and complement in and surrounding histologically spongiotic areas; these findings further correlated with increased levels of expression of Ki-67.

  20. Comparative study of the role of professional versus semiprofessional or nonprofessional antigen presenting cells in the rejection of vascularized organ allografts.

    Science.gov (United States)

    Sundstrom, J B; Ansari, A A

    1995-12-01

    for this phenomenon is the fact that cardiac myocytes do not constitutively express MHC class II molecules and express only low levels of class I molecules. However, this immunological unresponsiveness is maintained even after the induction of MHC class II and upregulation of MHC class I on these cells by interferon-gamma (IFN-gamma). Similar results have also been reported for cells of different tissue lineages (e.g. chondrocytes, keratinocytes, neural cells). Until now, cells have been defined as professional or nonprofessional for the purposes of defining their potential for antigen presentation to T cells. Professional antigen presenting cells have been identified as cells that are of haematopoietic origin, that constitutively express MHC class I and class II molecules as well as potent costimulatory molecules, and that are able to induce both primary and secondary immune responses, whereas nonprofessional antigen presenting cells are not bone marrow derived, do not constitutively express MHC class II, but may in some cases initiate primary and secondary immune responses after induction of MHC class II antigen by proinflammatory cytokines (e.g. IFN-gamma). The findings of our laboratory and others suggest that cells of certain lineages be considered in the separate class of 'nonantigen presenting cells'. Indeed, nonprofessional antigen presenting cells can be reclassified into three categories: semiprofessional-, nonprofessional-, or nonantigen presenting cells that are able to present antigen to and activate naive T cells, activated T cells, or no T Cells, respectively. The aim of this review is to identify and (re)examine the antigen presentation characteristics of cells of different tissue lineages in terms of their ability to activate different subsets of T cells. This approach is taken in an attempt to synthesize these concepts into a unified picture of T cell activation in the context of antigen processing and presentation by different cell types.

  1. Antigen presentation for priming T cells in central system.

    Science.gov (United States)

    Dasgupta, Shaoni; Dasgupta, Subhajit

    2017-01-01

    Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system. The recent approach towards circulating B-lymphocytes is an important area in the context. Here, we analyze the existing findings on antigen presentation in the central nervous system. The aim is to visualize signaling events of myelin antigen presentation to T cells and lead to the strategy of future goals on immunotherapy research.

  2. Self-antigen presentation by dendritic cells in autoimmunity

    Directory of Open Access Journals (Sweden)

    Ann-Katrin eHopp

    2014-02-01

    Full Text Available The operation of both central and peripheral tolerance ensures the prevention of autoimmune diseases. The maintenance of peripheral tolerance requires self-antigen presentation by professional antigen presenting cells (APCs. Dendritic cells (DCs are considered as major APCs involved in this process. The current review discusses the role of DCs in autoimmune diseases, the various factors involved in the induction and maintenance of tolerogenic DC phenotype and pinpoints their therapeutic capacity as well as potential novel targets for future clinical studies.

  3. Class II malocclusion occlusal severity description

    Directory of Open Access Journals (Sweden)

    Guilherme Janson

    2010-08-01

    Full Text Available OBJECTIVES: It is well known that the efficacy and the efficiency of a Class II malocclusion treatment are aspects closely related to the severity of the dental anteroposterior discrepancy. Even though, sample selection based on cephalometric variables without considering the severity of the occlusal anteroposterior discrepancy is still common in current papers. In some of them, when occlusal parameters are chosen, the severity is often neglected. The purpose of this study is to verify the importance given to the classification of Class II malocclusion, based on the criteria used for sample selection in a great number of papers published in the orthodontic journal with the highest impact factor. MATERIAL AND METHODS: A search was performed in PubMed database for full-text research papers referencing Class II malocclusion in the history of the American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO. RESULTS: A total of 359 papers were retrieved, among which only 72 (20.06% papers described the occlusal severity of the Class II malocclusion sample. In the other 287 (79.94% papers that did not specify the anteroposterior discrepancy severity, description was considered to be crucial in 159 (55.40% of them. CONCLUSIONS: Omission in describing the occlusal severity demands a cautious interpretation of 44.29% of the papers retrieved in this study.

  4. A role for NADPH oxidase in antigen presentation

    Directory of Open Access Journals (Sweden)

    Gail J Gardiner

    2013-09-01

    Full Text Available The nicotinamide adenine dinucleotide phosphate (NADPH oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.-. This radical is an important precursor of hydrogen peroxide (H2O2 and other reactive oxygen species (ROS needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD, a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC crosspresentation by major histocompatibility complex class I molecules (MHC-I through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules (MHC-II.

  5. Composition of MHC class II-enriched lipid microdomains is modified during maturation of primary dendritic cells.

    Science.gov (United States)

    Setterblad, Niclas; Roucard, Corinne; Bocaccio, Claire; Abastado, Jean-Pierre; Charron, Dominique; Mooney, Nuala

    2003-07-01

    Dendritic cells (DCs) are the most potent antigen presenting cells. Major histocompatibility complex (MHC) class II molecule expression changes with maturation; immature DCs concentrate MHC class II molecules intracellularly, whereas maturation increases surface expression of MHC class II and costimulatory molecules to optimize antigen presentation. Signal transduction via MHC class II molecules localized in lipid microdomains has been described in B lymphocytes and in the THP-1 monocyte cell line. We have characterized MHC class II molecules throughout human DC maturation with particular attention to their localization in lipid-rich microdomains. Only immature DCs expressed empty MHC class II molecules, and maturation increased the level of peptide-bound heterodimers. Ligand binding to surface human leukocyte antigen (HLA)-DR induced rapid internalization in immature DCs. The proportion of cell-surface detergent-insoluble glycosphingolipid-enriched microdomain-clustered HLA-DR was higher in immature DCs despite the higher surface expression of HLA-DR in mature DCs. Constituents of HLA-DR containing microdomains included the src kinase Lyn and the cytoskeletal protein tubulin in immature DCs. Maturation modified the composition of the HLA-DR-containing microdomains to include protein kinase C (PKC)-delta, Lyn, and the cytoskeletal protein actin, accompanied by the loss of tubulin. Signaling via HLA-DR redistributed HLA-DR and -DM and PKC-delta as well as enriching the actin content of mature DC microdomains. The increased expression of HLA-DR as a result of DC maturation was therefore accompanied by modification of the spatial organization of HLA-DR. Such regulation could contribute to the distinct responses induced by ligand binding to MHC class II molecules in immature versus mature DCs.

  6. Cross-dressing: an alternative mechanism for antigen presentation.

    Science.gov (United States)

    Campana, Stefania; De Pasquale, Claudia; Carrega, Paolo; Ferlazzo, Guido; Bonaccorsi, Irene

    2015-12-01

    Cross-dressing involves the transfer of preformed functional peptide-MHC complexes from the surface of donor cells to recipient cells, such as dendritic cells (DCs). These cross-dressed cells might eventually present the intact, unprocessed peptide-MHC complexes to T lymphocytes. In this review we will discuss some recent findings concerning the intercellular transfer of preformed MHC complexes and the possible mechanisms by which the transfer may occur. We will report evidences showing that both MHC class I and MHC class II functional complexes might be transferred, highlighting the physiological relevance of these cross-dressed cells for the presentation of exogenous antigens to both cytotoxic and helper T lymphocytes.

  7. Fibroblasts as Efficient Antigen-Presenting Cells in Lymphoid Organs

    Science.gov (United States)

    Kundig, Thomas M.; Bachmann, Martin F.; Dipaolo, Claudio; Simard, John J. L.; Battegay, Manuel; Lother, Heinz; Gessner, Andre; Kuhlcke, Klaus; Ohashi, Pamela S.; Hengartner, Hans; Zinkernagel, Rolf M.

    1995-06-01

    Only so-called "professional" antigen-presenting cells (APCs) of hematopoietic origin are believed capable of inducing T lymphocyte responses. However, fibroblasts transfected with viral proteins directly induced antiviral cytotoxic T lymphocyte responses in vivo, without involvement of host APCs. Fibroblasts induced T cells only in the milieu of lymphoid organs. Thus, antigen localization affects self-nonself discrimination and cell-based vaccine strategies.

  8. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

    Directory of Open Access Journals (Sweden)

    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  9. Condylar volume and condylar area in class I, class II and class III young adult subjects

    OpenAIRE

    Saccucci Matteo; D’Attilio Michele; Rodolfino Daria; Festa Felice; Polimeni Antonella; Tecco Simona

    2012-01-01

    Abstract Aim Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. Material and methods 200 Caucasian patients (15–30 years old, 95 male and 105 females) were classified in three groups on the base of ANB angle: skeletal class I (65 patients), skeletal class II (70 patients) and skeletal class III (65 patients). Left and right TMJs of each subject were evaluated independently with CBCT (Iluma). ...

  10. Interleukin 10 (IL-10)-mediated Immunosuppression: MARCH-I INDUCTION REGULATES ANTIGEN PRESENTATION BY MACROPHAGES BUT NOT DENDRITIC CELLS.

    Science.gov (United States)

    Mittal, Sharad K; Cho, Kyung-Jin; Ishido, Satoshi; Roche, Paul A

    2015-11-06

    Efficient immune responses require regulated antigen presentation to CD4 T cells. IL-10 inhibits the ability of dendritic cells (DCs) and macrophages to stimulate antigen-specific CD4 T cells; however, the mechanisms by which IL-10 suppresses antigen presentation remain poorly understood. We now report that IL-10 stimulates expression of the E3 ubiquitin ligase March-I in activated macrophages, thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells. By contrast, IL-10 does not stimulate March-I expression in DCs, does not suppress MHC-II or CD86 expression on either resting or activated DCs, and does not affect antigen presentation by activated DCs. IL-10 does, however, inhibit the process of DC activation itself, thereby reducing the efficiency of antigen presentation in a March-I-independent manner. Thus, IL-10 suppression of antigen presenting cell function in macrophages is March-I-dependent, whereas in DCs, suppression is March- I-independent.

  11. 46 CFR 50.30-15 - Class II pressure vessels.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Class II pressure vessels. 50.30-15 Section 50.30-15... Fabrication Inspection § 50.30-15 Class II pressure vessels. (a) Class II pressure vessels shall be subject to... pressure vessels shall be performed during the welding of the longitudinal joint. At this time the...

  12. 49 CFR 238.317 - Class II brake test.

    Science.gov (United States)

    2010-10-01

    ... locomotives that utilize an electric signal to communicate a service brake application and only a pneumatic... 49 Transportation 4 2010-10-01 2010-10-01 false Class II brake test. 238.317 Section 238.317... Requirements for Tier I Passenger Equipment § 238.317 Class II brake test. (a) A Class II brake test shall...

  13. MHC structure and function – antigen presentation. Part 1

    Science.gov (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function. PMID:25807245

  14. Lateral cephalometric diagnosis of asymmetry in Angle Class II subdivision compared to Class I and II

    Directory of Open Access Journals (Sweden)

    Aparecida Fernanda Meloti

    2014-08-01

    Full Text Available INTRODUCTION: Lateral cephalometric radiographs are traditionally required for orthodontic treatment, yet rarely used to assess asymmetries. OBJECTIVE: The objective of the present study was to use lateral cephalometric radiographs to identify existing skeletal and dentoalveolar morphological alterations in Class II subdivision and to compare them with the existing morphology in Class I and II relationship. MATERIAL AND METHODS: Ninety initial lateral cephalometric radiographs of male and female Brazilian children aged between 12 to 15 years old were randomly and proportionally divided into three groups: Group 1 (Class I, Group 2 (Class II and Group 3 (Class II subdivision. Analysis of lateral cephalometric radiographs included angular measurements, horizontal linear measurements and two indexes of asymmetry that were prepared for this study. RESULTS: In accordance with an Index of Dental Asymmetry (IDA, greater mandibular dental asymmetry was identified in Group 3. An Index of Mandibular Asymmetry (IMA revealed less skeletal and dental mandibular asymmetry in Group 2, greater skeletal mandibular asymmetry in Group 1, and greater mandibular dental asymmetry in Group 3. CONCLUSION: Both IDA and IMA revealed greater mandibular dental asymmetry for Group 3 in comparison to Groups 1 and 2. These results are in accordance with those found by other diagnostic methods, showing that lateral cephalometric radiography is an acceptable method to identify existing skeletal and dentoalveolar morphological alterations in malocclusions.

  15. Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles

    Science.gov (United States)

    Sayour, Elias J.; Pham, Christina; Grippin, Adam; Kemeny, Hanna; Chua, Joshua; Sampson, John H.; Sanchez-Perez, Luis; Flores, Catherine; Mitchell, Duane A.

    2017-01-01

    ABSTRACT While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction. We screened commercially available nanoliposomal preparations and identified the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as an efficient mRNA courier to antigen-presenting cells (APCs). When administered intravenously, RNA-NPs mediate systemic activation of APCs in reticuloendothelial organs such as the spleen, liver, and bone marrow. RNA-NPs increase percent expression of MHC class I/II, B7 co-stimulatory molecules, and maturation markers on APCs (all vital for T-cell activation). RNA-NPs also increase activation markers on tumor APCs and elicit potent expansion of antigen-specific T-cells superior to peptide vaccines formulated in complete Freund's adjuvant. We demonstrate that both model antigen-encoding and physiologically-relevant tumor-derived RNA-NPs expand potent antitumor T-cell immunity. RNA-NPs were shown to induce antitumor efficacy in a vaccine model and functioned as a suitable alternative to DCs in a stringent cellular immunotherapy model for a radiation/temozolomide resistant invasive murine high-grade glioma. Although cancer vaccines have suffered from weak immunogenicity, we have advanced a RNA-NP formulation that systemically activates host APCs precipitating activated T-cell frequencies necessary to engender antitumor efficacy. RNA-NPs can thus be harnessed as a more feasible and effective immunotherapy to re-program host-immunity. PMID:28197373

  16. Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells.

    Science.gov (United States)

    Becker, Hans Jiro; Kondo, Eisei; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; von Bergwelt-Baildon, Michael S

    2016-08-01

    Activated B cells have the capacity to present antigen and induce immune responses as potent antigen-presenting cells (APCs). As in other APCs, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto MHC molecules. However, while the mechanism of antigen processing has been studied extensively in other APCs, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD40-activated B cells (CD40Bs), as a model for activated, antigen-presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD4 + T-cell epitope 509-523 (K509) by human CD40Bs in ELISPOT assays. As expected, stimulation of specific CD4 + T-cell clones was attenuated after pretreatment of CD40Bs with inhibitors of classic class II pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non-classical, cytosolic MHC class II pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in CD40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this APC. Our data suggest that B cells process antigen using a distinct, non-classical class II pathway.

  17. MHC class II molecules regulate growth in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K;

    1994-01-01

    lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1......MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

  18. The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.

    Science.gov (United States)

    Andersson, Lisa S; Swinburne, June E; Meadows, Jennifer R S; Broström, Hans; Eriksson, Susanne; Fikse, W Freddy; Frey, Rebecka; Sundquist, Marie; Tseng, Chia T; Mikko, Sofia; Lindgren, Gabriella

    2012-03-01

    Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p (raw) = 2.34 × 10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.

  19. Condylar volume and condylar area in class I, class II and class III young adult subjects

    Directory of Open Access Journals (Sweden)

    Saccucci Matteo

    2012-12-01

    Full Text Available Abstract Aim Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. Material and methods 200 Caucasian patients (15–30 years old, 95 male and 105 females were classified in three groups on the base of ANB angle: skeletal class I (65 patients, skeletal class II (70 patients and skeletal class III (65 patients. Left and right TMJs of each subject were evaluated independently with CBCT (Iluma. TMJ evaluation included: condylar volume; condylar area; morphological index (MI. Condylar volumes were calculated by using the Mimics software. The condylar volume, the area and the morphological index (MI were compared among the three groups, by using non-parametric tests. Results The Kruskal-Wallis test and the Mann Whitney test revealed that: no significant difference was observed in the whole sample between the right and the left condylar volume; subjects in skeletal class III showed a significantly higher condylar volume, respect to class I and class II subjects (p 3 in males and 663.5 ± 81.3 mm3 in females; p 2 in males and 389.76 ± 61.15 mm2 in females; p  Conclusion Skeletal class appeared to be associated to the mandibular condylar volume and to the mandibular condylar area in the Caucasian orthodontic population.

  20. Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Jung-Ok Kang

    Full Text Available Cholera toxin (CT, an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN. Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT-treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1β, and activin A had a synergic role with TGF-β1 in CT-mediated Th17 cell differentiation. Taken together, our results suggest that CT-stimulated DCs promote Th17 cell differentiation by not only modulating antigen-presenting potential but also inducing Th polarizing cytokines.

  1. Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells

    Science.gov (United States)

    Kang, Jung-Ok; Lee, Jee-Boong

    2016-01-01

    Cholera toxin (CT), an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC) populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN). Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT-treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1β, and activin A had a synergic role with TGF-β1 in CT-mediated Th17 cell differentiation. Taken together, our results suggest that CT-stimulated DCs promote Th17 cell differentiation by not only modulating antigen-presenting potential but also inducing Th polarizing cytokines. PMID:27271559

  2. Toward a network model of MHC class II-restricted antigen processing

    Directory of Open Access Journals (Sweden)

    Laurence C Eisenlohr

    2013-12-01

    Full Text Available The standard model of Major Histocompatibility Complex class II (MHCII-restricted antigen processing depicts a straightforward, linear pathway: Internalized antigens are converted into peptides that load in a chaperone dependent manner onto nascent MHCII in the late endosome, the complexes subsequently trafficking to the cell surface for recognition by CD4+ T cells (TCD4+. Several variations on this theme, both moderate and radical, have come to light but these alternatives have remained peripheral, the conventional pathway generally presumed to be the primary driver of TCD4+ responses. Here we continue to press for the conceptual repositioning of these alternatives toward the center while proposing that MHCII processing be thought of less in terms of discrete pathways and more in terms of a network whose major and minor conduits are variable depending upon many factors, including the epitope, the nature of the antigen, the source of the antigen, and the identity of the antigen-presenting cell.

  3. Angle Class II correction with MARA appliance

    Directory of Open Access Journals (Sweden)

    Kelly Chiqueto

    2013-02-01

    Full Text Available OBJECTIVE: To assess the effects produced by the MARA appliance in the treatment of Angle's Class II, division 1 malocclusion. METHODS: The sample consisted of 44 young patients divided into two groups: The MARA Group, with initial mean age of 11.99 years, treated with the MARA appliance for an average period of 1.11 years, and the Control Group, with initial mean age of 11.63 years, monitored for a mean period of 1.18 years with no treatment. Lateral cephalograms were used to compare the groups using cephalometric variables in the initial and final phases. For these comparisons, Student's t test was employed. RESULTS: MARA appliance produced the following effects: Maxillary growth restriction, no change in mandibular development, improvement in maxillomandibular relationship, increased lower anterior facial height and counterclockwise rotation of the functional occlusal plane. In the upper arch, the incisors moved lingually and retruded, while the molars moved distally and tipped distally. In the lower arch, the incisors proclined and protruded, whereas the molars mesialized and tipped mesially. Finally, there was a significant reduction in overbite and overjet, with an obvious improvement in molar relationship. CONCLUSIONS: It was concluded that the MARA appliance proved effective in correcting Angle's Class II, division 1 malocclusion while inducing skeletal changes and particularly dental changes.OBJETIVO: avaliar os efeitos proporcionados pelo aparelho MARA no tratamento da má oclusão de Classe II, 1ª divisão. MÉTODOS: utilizou-se uma amostra de 44 jovens, divididos em dois grupos - Grupo MARA, com idade inicial média de 11,99 anos e tratado com o aparelho MARA por um período médio de 1,11 ano; e Grupo Controle, com idade inicial média de 11,63 ano e observado por um período médio de 1,18 ano, sem nenhum tratamento. Utilizou-se as telerradiografias em norma lateral para comparar os grupos quanto às variáveis cefalométricas das

  4. Heterodimeric barnase-barstar vaccine molecules: influence of one versus two targeting units specific for antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Heidi Cecilie Larsen Spång

    Full Text Available It is known that targeting of antigen to antigen presenting cells (APC increases immune responses. However, it is unclear if more than one APC-specific targeting unit in the antigenic molecule will increase responses. To address this issue, we have here made heterodimeric vaccine molecules that each express four different fusion subunits. The bacterial ribonuclease barnase and its inhibitor barstar interact with high affinity, and the barnase-barstar complex was therefore used as a dimerization unit. Barnase and barstar were fused N-terminally with single chain fragment variable (scFvs targeting units specific for either MHC class II molecules on APC or the hapten 5-iodo-4-hydroxy-3-nitrophenylacetyl (NIP. C-terminal antigenic fusions were either the fluorescent protein mCherry or scFv(315 derived from myeloma protein M315. The heterodimeric vaccine molecules were formed both in vitro and in vivo. Moreover, the four different fused moieties appeared to fold correctly since they retained their specificity and function. DNA vaccination with MHC class II-targeted vaccine induced higher mCherry-specific IgG1 responses compared to non-targeted control. Since mCherry and MHC class II are in trans in this heterodimer, this suggests that heterodimeric proteins are formed in vivo without prior protein purification. Surprisingly, one targeting moiety was sufficient for the increased IgG1 response, and addition of a second targeting moiety did not increase responses. Similar results were found in in vitro T cell assays; vaccine molecules with one targeting unit were as potent as those with two. In combination with the easy cloning strategy, the heterodimeric barnase-barstar vaccine molecule could provide a flexible platform for development of novel DNA vaccines with increased potency.

  5. Identifying a Small Molecule Blocking Antigen Presentation in Autoimmune Thyroiditis.

    Science.gov (United States)

    Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron

    2016-02-19

    We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD.

  6. Activation of human T cells by major histocompatability complex class II expressing neutrophils: proliferation in the presence of superantigen, but not tetanus toxoid.

    Science.gov (United States)

    Fanger, N A; Liu, C; Guyre, P M; Wardwell, K; O'Neil, J; Guo, T L; Christian, T P; Mudzinski, S P; Gosselin, E J

    1997-06-01

    The primary function of polymorphonuclear neutrophils (PMN) in the immune response appears to be acute phagocytic clearance of foreign pathogens and release of inflammatory mediators. Consistent with their assumed lack of major histocompatibility complex (MHC) class II expression, PMN have not been considered to play a role in antigen presentation and T-cell activation. However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). Thus, under appropriate conditions, PMN could play a significant role in immune regulation, including T-cell activation. In this report, we demonstrate that human class II-expressing PMN can serve as accessory cells in superantigen (SAg)-mediated T-cell activation. This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN. Moreover, the level of MHC class II expression and the magnitude of SAg-induced T-cell responses were found to be highly correlated and distinctly donor dependent, with PMN from some donors repeatedly showing fivefold higher responses than PMN from other donors. On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide. These results delineate a new pathway for T-cell activation by SAg that may play an important role in the severity of SAg-induced inflammatory responses. They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.

  7. Engagement of major histocompatibility complex class I and class II molecules up-regulates intercellular adhesion of human B cells via a CD11/CD18-independent mechanism.

    Science.gov (United States)

    Alcover, A; Juillard, V; Acuto, O

    1992-02-01

    We have studied the role of major histocompatibility complex (MHC) molecules in the regulation of intercellular adhesion of human B cells. We found that molecules able to bind to MHC class II molecules, such as monoclonal antibodies or staphylococcal enterotoxins, induced rapid and sustained homotypic adhesion of Epstein-Barr virus (EBV)-transformed B cell lines as well as peripheral blood B lymphocytes. Moreover, anti-MHC class I monoclonal antibodies also stimulated intercellular adherence. Adhesion induced upon MHC engagement was faster and stronger than that triggered by phorbol esters. It needed active metabolism, but divalent cations were not required. Monoclonal antibodies directed against LFA-1 (CD11a/CD18) or its ligand ICAM-1 (CD54) did not inhibit MHC class II-induced homotypic adhesion of various EBV-transformed B cell lines, nor of a variant of the B cell line Raji expressing very low LFA-1 surface levels. Moreover, EBV-transformed B cells from a severe lymphocyte adhesion deficiency patient, lacking surface CD11/CD18, also aggregated in response to anti-MHC class I or class II monoclonal antibodies. Together these data indicate that engagement of MHC molecules may transduce signals to B cells resulting in up-regulation of intercellular adhesion, via an LFA-1-independent mechanism. This may play a role in the stabilization of T cell/antigen-presenting cell conjugates at the moment of antigen recognition.

  8. Freezing and thawing of murine bone marrow-derived dendritic cells does not alter their immunophenotype and antigen presentation characteristics.

    Science.gov (United States)

    Mendoza, L; Bubeník, J; Indrová, M; Bieblová, J; Vonka, V; Símová, J

    2002-01-01

    The aim of this paper was to assess whether the BMDC after freezing and thawing are capable to retain the immunophenotype and antigen-presenting capacity. BMDC were generated from bone marrow precursor cells as described previously by culturing the cells in medium containing GM-CSF and IL-4. Afterwards, the cells were harvested, counted and used for phenotyping and priming of syngeneic spleen cells. For cryopreservation, the BMDC were frozen in the presence of 10% of dimethylsulphoxide (DMSO) and 90% foetal calf serum. Forty to fifty percent of both samples, frozen/thawed as well as fresh BMDC, exhibited characteristic DC morphology, and the DC obtained from the frozen/thawed samples expressed a similar level of MHC class I-, MHC class II-, CD80-, CD86-, CD11c-, CD11b-, CD54- and CD205-molecule as fresh DC. To examine the in vitro priming effect of cryopreserved BMDC on syngeneic non-adherent murine C57BL/6 (B6) spleen cells, the BMDC were thawed, pulsed with the lysate prepared from HPV 16-associated tumour MK16 and used for 3H-thymidine assay. The findings of the experiments indicate that fresh as well as cryopreserved murine BMDC preparations pulsed with tumour lysate were efficient to prime the mitogenic activity of syngeneic non-adherent splenocytes. Taken together, the results suggest that frozen/thawed BMDC are morphologically, phenotypically and functionally comparable with fresh BMDC and can be used for construction of dendritic cell-based tumour vaccines.

  9. Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer.

    Science.gov (United States)

    Surmann, Eva-Maria; Voigt, Anita Y; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Ferrone, Soldano; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2015-03-01

    Besides being expressed on professional antigen-presenting cells, HLA class II antigens are expressed on various tumors of non-lymphoid origin, including a subset of colorectal cancers (CRC). Information about the regulation of HLA class II antigen expression is important for a better understanding of their role in the interactions between tumor and immune cells. Whether lack of HLA class II antigen expression in tumors reflects the selective immune destruction of HLA class II antigen-expressing tumor cells is unknown. To address this question, we tested whether lack of HLA class II antigen expression in CRC was associated with immune cell infiltration. We selected microsatellite-unstable (MSI-H) CRC, because they show pronounced tumor antigen-specific immune responses and, in a subset of tumors, lack of HLA class II antigen expression due to mutations inactivating HLA class II-regulatory genes. We examined HLA class II antigen expression, mutations in regulatory genes, and CD4-positive T cell infiltration in 69 MSI-H CRC lesions. Mutations in RFX5, CIITA, and RFXAP were found in 13 (28.9%), 3 (6.7%), and 1 (2.2%) out of 45 HLA class II antigen-negative tumors. CD4-positive tumor-infiltrating lymphocyte counts were significantly higher in HLA class II antigen-negative tumors harboring mutations in HLA class II-regulatory genes (107.4 T cells per 0.25 mm(2)) compared to tumors without mutations (55.5 T cells per 0.25 mm(2), p = 0.008). Our results suggest that the outgrowth of tumor cells lacking HLA class II antigen expression due to mutations of regulatory genes is favored in an environment of dense CD4-positive T cell infiltration.

  10. Early Intervention in Skeletal Class II and dental Class II division I malocclusion

    Directory of Open Access Journals (Sweden)

    Zeeshan Iqbal Bhat

    2013-01-01

    Full Text Available A Class II malocclusion may occur as a result of mandibular deficiency, maxillary excess, or a combination of both. However, the most common finding is mandibular skeletal retrusion. The use of functional jaw orthopedics, at the right time during growth, can ultimately result in malocclusion patients achieving an excellent functional occlusion, a broad beautiful smile, a full face with a beautiful jaw line, and profile. Functional jaw orthopedic (FJO appliances are designed to encourage adaptive skeletal growth by maintaining the mandible in a corrected forward position. The activator developed by Andresen is one of the most widely used for this purpose. A 12-year-old boy with skeletal Class II malocclusion and dental Class II div I malocclusion, a low mandibular plane angle was treated with growth modulation using an activator followed by molar distalization using fixed orthodontics for detailing of the occlusion. The major effects of the activator treatment in this case have been due to increase in condylar growth and also an increase in mandibular base length. Further, non-extraction fixed orthodontic treatment for proper interdigitation of the dentition also helped to maintain the stability of the satisfactory results achieved.

  11. Modes of Antigen Presentation by Lymph Node Stromal Cells and Their Immunological Implications.

    Science.gov (United States)

    Hirosue, Sachiko; Dubrot, Juan

    2015-01-01

    Antigen presentation is no longer the exclusive domain of cells of hematopoietic origin. Recent works have demonstrated that lymph node stromal cell (LNSC) populations, such as fibroblastic reticular cells, lymphatic and blood endothelial cells, not only provide a scaffold for lymphocyte interactions but also exhibit active immunomodulatory roles that are critical to mounting and resolving effective immune responses. Importantly, LNSCs possess the ability to present antigens and establish antigen-specific interactions with T cells. One example is the expression of peripheral tissue antigens, which are presented on major histocompatibility complex (MHC)-I molecules with tolerogenic consequences on T cells. Additionally, exogenous antigens, including self and tumor antigens, can be processed and presented on MHC-I complexes, which result in dysfunctional activation of antigen-specific CD8(+) T cells. While MHC-I is widely expressed on cells of both hematopoietic and non-hematopoietic origins, antigen presentation via MHC-II is more precisely regulated. Nevertheless, LNSCs are capable of endogenously expressing, or alternatively, acquiring MHC-II molecules. Transfer of antigen between LNSC and dendritic cells in both directions has been recently suggested to promote tolerogenic roles of LNSCs on the CD4(+) T cell compartment. Thus, antigen presentation by LNSCs is thought to be a mechanism that promotes the maintenance of peripheral tolerance as well as generates a pool of diverse antigen-experienced T cells for protective immunity. This review aims to integrate the current and emerging literature to highlight the importance of LNSCs in immune responses, and emphasize their role in antigen trafficking, retention, and presentation.

  12. Class II transactivator (CIITA enhances cytoplasmic processing of HIV-1 Pr55Gag.

    Directory of Open Access Journals (Sweden)

    Kristen A Porter

    Full Text Available BACKGROUND: The Pr55(gag (Gag polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs. In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol (Gag-Pol levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.

  13. 25 CFR 522.10 - Individually owned class II and class III gaming operations other than those operating on...

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II and class III gaming... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.10 Individually owned class II and class...

  14. Hypothesis: Targeted Ikkβ deletion upregulates MIF signaling responsiveness and MHC class II expression in mouse hepatocytes

    Directory of Open Access Journals (Sweden)

    Katherine S Koch

    2010-03-01

    Full Text Available Katherine S Koch, Hyam L LeffertHepatocyte Growth Control and Stem Cell Laboratory, Department of Pharmacology, School of Medicine, University of California, San Diego, CA, USAAbstract: Macrophage migration inhibitory factor (MIF is causally related to the pathogenesis of chronic liver disease but its hepatocellular mechanisms of action are largely unknown. Scattered reports in the literature hint at functional connections between the expression of MIF and major histocompatibility complex (MHC Class II molecules. Not surprisingly, these relationships have not yet been explored in hepatocytes because MIF and MHC Class II cell surface receptors are commonly expressed by other cell types including various antigen presenting cells of the immune system. On the other hand, mounting evidence suggests that heteromeric MIF receptors share a common molecule with intracellular MHC Class II complexes, viz., CD74, which also serves as the MHC Class II chaperone; and, while it is unclear what cancer-related role(s MHC Class II receptors might play, increasing evidence suggests that MIF and CD74 are also implicated in the biology of hepatocellular carcinoma. These reports are provocative for two reasons: firstly, Ikkβ Δhep mice carrying hepatocyte-targeted deletions of Ikkβ, an IκB kinase complex subunit required for the activation of the transcription factor NF-κB (nuclear factor-κB, have been shown to display heightened susceptibilities to hepatotoxins and chemical hepatocarcinogens; secondly, microarray profiling observations indicate that Ikkβ Δhep hepatocytes constitutively and “ectopically” overexpress genes, particularly CD74, CD44 (a MIF-receptor subunit and MHC Class II I-A/E β and I-A α chains, and gene families that regulate host immune process and immune defense responses. These findings together suggest that Ikkβ Δhep mice might express functional MIF and MHC Class II receptors, leading to increased hepatocellular sensitivity to

  15. HLA Class I and Class II Associations with ESRD in Saudi Arabian Population

    OpenAIRE

    Nuha Mahmoud Hamdi; Fadel Hassan Al-Hababi; Amr Ekhlas Eid

    2014-01-01

    BACKGROUND: Chronic renal failure (CRF) leads in the majority of instances to end stage renal disease (ESRD) requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population. METHODOLOGY: A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated ...

  16. Class II correction prior to orthodontics with the carriere distalizer.

    Science.gov (United States)

    McFarlane, Bruce

    2013-01-01

    Class II correction is a challenge in orthodontics with many existing devices being complex, too compliance-driven, or too prone to breakage. The Carriere Distalizer allows for straightforward Class II correction prior to orthodontics (fixed or clear aligners) at a time when no other mechanics interfere, and compliance is at its best.

  17. Dentofacial characteristics of patients with Angle Class I and Class II malocclusions

    Directory of Open Access Journals (Sweden)

    Rogério Lacerda dos Santos

    2012-04-01

    Full Text Available OBJECTIVE: The present study assessed some cephalometric measurements of the soft tissue profile in order to observe the behavior of facial convexity in patients with Class I, Class II division 1, and Class II division 2 malocclusions. METHODS: One hundred and thirty pre-treatment teleradiographs of Caucasian patients aged 10-16 years (mean age of 12.6 years were selected for study and divided into 3 groups. The cephalometric measurements used in the present study were the following: H.SN, Cx, NLA, MLA, UL-SUL-S, LL-S, IMPA, and 1-SN. Analysis of variance and Tukey's test were applied for measurements H.SN, Cx, IMPA, 1-SN, MLA, and NLA, whereas Kruskal-Wallis and Dunn's tests were applied for UL-S and LL-S. RESULTS: The results showed statistically significant differences for the measurements H.SN, Cx, UL-S, and IMPA between Groups I, II-1 and II-2 (p < 0.05. Measurements LL-S and MLA showed statistically significant difference between Groups I and II-1 only (p < 0.05. On the other hand, no statistically significant differences were found for measurement NLA among the 3 groups (p < 0.05. CONCLUSION: Regarding facial characteristics expressed by measurements H.SN, Cx, and UL-S, one could conclude that Class II division 1 and Class II division 2 malocclusions, both differed from Class I malocclusion. In addition, Class II division 1 malocclusion was found to have facial characteristics expressed by MLA, which differentiate it from the Class II division 2 and Class 1 malocclusions. Class I, Class II division 1 and Class II division 2 malocclusions showed no difference in facial characteristics expressed by the measurement NLA, and measurement LL-S was directly related to eversion of the lower lip.

  18. Signalling via MHC class II molecules modifies the composition of GEMs in APC.

    Science.gov (United States)

    Setterblad, N; Becart, S; Charron, D; Mooney, N

    2001-01-01

    Major histocompatibility complex (MHC) class II molecules are responsible for peptide presentation to helper T lymphocytes and as such play an essential role in the immune response. These molecules transmit intracellular signals leading to diverse consequences in B lymphocytes including proliferation and apoptosis. Recent studies have revealed that glycolipid enriched membrane microdomains (GEMs) behave as signalling platforms for a variety of lymphocyte receptors. We have quantified human leucocyte antigen (HLA)-DR molecules localized in GEMs in human B lymphocytes. Use of a model imitating the interaction of HLA-DR with a T-cell receptor (TCR) modified the constituents of the HLA-DR-enriched GEMs. Confocal microscopy demonstrated a recruitment of HLA-DR and the ganglioside GM1 at the site of HLA-DR interaction with the stimulating ligand. Moreover, cholesterol depletion efficiently impaired this recruitment. Co-localizing proteins detected in HLA-DR-enriched GEMs include protein kinase C (PKC)-delta and actin. These data reveal that MHC class II antigens are localized in GEMs in mature human B lymphocytes and indicates that the formation of the immunological synapse regulates the composition of HLA-DR enriched GEMs in the antigen presenting cell (APC).

  19. No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.

    Directory of Open Access Journals (Sweden)

    Slobodan Culina

    Full Text Available Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently insulin-degrading enzyme (IDE was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of IDE in MHC class I antigen processing. Here we report that IDE knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent IDE expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred IDE substrates. Thus, IDE does not play a major role in MHC class I antigen processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.

  20. No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.

    Science.gov (United States)

    Culina, Slobodan; Mauvais, François-Xavier; Hsu, Hsiang-Ting; Burgevin, Anne; Guénette, Suzanne; Moser, Anna; van Endert, Peter

    2014-01-01

    Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently insulin-degrading enzyme (IDE) was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of IDE in MHC class I antigen processing. Here we report that IDE knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent IDE expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred IDE substrates. Thus, IDE does not play a major role in MHC class I antigen processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.

  1. Antigen-presenting cells in parotid glands contain cystatin D originating from acinar cells.

    Science.gov (United States)

    Nashida, Tomoko; Sato, Ritsuko; Haga-Tsujimura, Maiko; Yoshie, Sumio; Yoshimura, Ken; Imai, Akane; Shimomura, Hiromi

    2013-02-01

    Cystatin D encoded by Cst5 is a salivary classified type II cystatin. We investigated the dynamism of cystatin D by examining the distribution of cystatin D protein and mRNA in rats, to identify novel functions. The simultaneous expression of Cst5 and cystatin D was observed in parotid glands, however in situ hybridization showed that only acinar cells produced cystatin D. Synthesized cystatin D was localized in small vesicles and secreted from the apical side to the saliva, and from the basolateral side to the extracellular region, a second secretory pathway for cystatin D. We also identified antigen-presenting cells in the parotid glands that contained cystatin D without the expression of Cst5, indicating the uptake of cystatin D from the extracellular region. Cystatin D was detected in blood serum and renal tubular cells with megalin, indicating the circulation of cystatin D through the body and uptake by renal tubular cells. Thus, the novel dynamism of cystatin D was shown and a function for cystatin D in the regulation of antigen-presenting cell activity was proposed.

  2. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4{sup +} intestinal intraepithelial lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru, E-mail: atotuka@mail.ecc.u-tokyo.ac.jp

    2013-06-14

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.

  3. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

    Science.gov (United States)

    Buschow, Sonja I; van Balkom, Bas W M; Aalberts, Marian; Heck, Albert J R; Wauben, Marca; Stoorvogel, Willem

    2010-01-01

    Professional antigen-presenting cells secrete major histocompatibility complex class II (MHC II) carrying exosomes with unclear physiological function(s). Exosomes are first generated as the intraluminal vesicles (ILVs) of a specific type of multivesicular body, and are then secreted by fusion of this compartment with the plasma membrane. We have previously shown that in contrast to the sorting of MHC II at lysosomally targeted multivesicular bodies, sorting of MHC II into exosomes does not rely on MHC II ubiquitination. In search for proteins that drive the incorporation of MHC II into exosomes or functionally discriminate exosomal from plasma membrane MHC II, we first analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins, including known and not previously identified constituents. Using quantitative MS, we then identified a small subset of proteins that were specifically co-immunoprecipitated with MHC II from detergent-solubilized exosomes. These include HSC71, HSP90, 14-3-3ɛ, CD20 and pyruvate kinase type M2 (PKM2), and we speculate on the functionality of their interaction with exosomal MHC II.

  4. Archform comparisons between skeletal class II and III malocclusions.

    Science.gov (United States)

    Zou, Wei; Wu, JiaQi; Jiang, JiuHui; Xu, TianMin; Li, CuiYing

    2014-01-01

    The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2) and Skeletal Class III (SC3) malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group) and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crown)and WALA points (the most prominent point on the soft-tissue ridge)were employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2). In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

  5. The simple class II and class III corrector: three case reports.

    Science.gov (United States)

    Spary, David John; Little, Rachel Ann

    2015-03-01

    This article illustrates three case reports which describe a very simple appliance that is used to correct both class II and class III buccal segments. A class I molar relationship is achieved within 2-6 months. Hundreds of cases have been treated with these appliances over a number of years at Queen's Hospital, Burton upon Trent with great success.

  6. Class II barodontalgia: review and report of a case.

    Science.gov (United States)

    Woodmansey, Karl

    2008-01-01

    Barodontalgia is a rarely reported condition involving changes in ambient pressure resulting in tooth pain. According to Ferjentsik and Aker, Class II barodontalgia is observed in teeth that have pre-existing pulpal disease and an ultimate diagnosis of irreversible pulpitis.1 This article describes a case of Class II barodontalgia that was experienced on a commercial airline flight and reviews current knowledge regarding this phenomenon, including proposed etiologic mechanisms.

  7. An in situ hybridization study of the effects of artificial insemination on the localization of cells expressing MHC class II mRNA in the chicken oviduct.

    Science.gov (United States)

    Zheng, W M; Nishibori, M; Isobe, N; Yoshimura, Y

    2001-10-01

    The aim of this study was to determine the effects of artificial insemination on the localization of antigen-presenting cells expressing MHC class II mRNA in chicken oviducts. Laying hens (35 weeks old) were inseminated with fresh semen or sham-inseminated with saline daily for 3 days. In situ hybridization was performed to detect chicken MHC class II (B-LB21 major gene) mRNA on frozen sections of oviductal infundibulum, uterovaginal junction and vagina by using digoxigenin-labelled PCR probes. Cells expressing MHC class II were observed mainly in the oviductal mucosal stroma and occasionally in the mucosal epithelium. After 24 h, the population of cells expressing MHC class II in the infundibulum was significantly higher in laying hens inseminated with fresh semen than in the control hens sham-inseminated with saline (P artificially inseminated and control hens. These results indicate that anti-sperm immune responses, including the influx of cells expressing MHC class II and enhanced MHC class II mRNA expression, probably occur in the infundibulum after artificial insemination.

  8. NLRC5, AT THE HEART OF ANTIGEN PRESENTATION

    Directory of Open Access Journals (Sweden)

    Andreas eNeerincx

    2013-11-01

    Full Text Available Nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs are intracellular proteins mainly involved in pathogen recognition, inflammatory responses, and cell death. Until recently, the function of the family member NLR caspase recruitment domain (CARD containing 5 (NLRC5 has been a matter of debate. It is now clear that NLRC5 acts as a transcriptional regulator of the major-histocompatibility complex (MHC class I. In this review we detail the development of our understanding of NLRC5 function, discussing both the accepted and the controversial aspects of NLRC5 activity. We give insight into the molecular mechanisms, and the potential implications, of NLRC5 function in health and disease.

  9. The CLASS blazar survey - II. Optical properties

    NARCIS (Netherlands)

    Caccianiga, A; Marcha, MJ; Anton, S; Mack, KH; Neeser, MJ

    2002-01-01

    This paper presents the optical properties of the objects selected in the CLASS blazar survey. Because an optical spectrum is now available for 70 per cent of the 325 sources present in the sample, a spectral classification, based on the appearance of the emission/absorption lines, is possible. A wi

  10. An Investigation of Craniocervical Posture in Class II & Class III Skeletal Patients

    Directory of Open Access Journals (Sweden)

    T. HoseinZadeh-Nik

    2005-02-01

    Full Text Available Statement of Problem: Craniocervical Posture is a factor in the development and function of Craniofacial Structure. Previous studies of different samples have demonstrated associations between craniocervical posture and craniofacial morphology.Purpose: This study aimed lo examine whether any significant association is evident or not between craniocervical posture and the occurrence of Class il & Class III skeletal malocclusions.Materials and Methods: A sample of 76 subjects with Class II & Class III skeletal malocclusion aged 9-i 1 and>18 years were selected. None of them had received orthodontic treatment. Lateral cephalometric radiographs were taken in natural head position (NHP, and craniocervical and craniohorizental angels were traced and determined for analysis of craniocervical posture. Results: According to the craniocervical posture, most class II skeletal patients have flexed heads and class MI skeletal patients have extended heads, as a result malocclusion in these patients seems to become more severe. With increase in age. class II skeletal patients have more flexed their heads and malocclusion become more severe, while with increase in age in class ill skeletal patients, their heads become extended and once again malocclusion thought lo be more severe. In class II skeletal patients, craniocervical posture has a significant correlation with the vertical growth pattern, but shows little correlation with the horizontal growth pattern. In class 111 skeletal patients, craniocervical posture shows no correlation to any of the vertical & horizontal growth patterns, of course the mean of vertical angles is less in these patients and probably in order to make these relation significant in Class III skeletal patients there is need for more samples, in class II & class III skeletal patients, the amount of Na.prep-point A and pog-Na.prep with craniocervical posture shows a significant correlation. Conclusion: Consideration of craniocervical

  11. MHC Class II epitope predictive algorithms

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lund, Ole; Buus, S

    2010-01-01

    reasonably accurate predictions for alleles that were not included in the training data. These methods can be used to define supertypes (clusters) of MHC-II alleles where alleles within each supertype have similar binding specificities. Furthermore, the pan-specific methods have been used to make a graphical...

  12. DNA polymorphism of HLA class II genes in alopecia areata

    DEFF Research Database (Denmark)

    Morling, N; Frentz, G; Fugger, L;

    1992-01-01

    of the serologically defined HLA-DQw7 specificity. Individuals who carried both DQA1*0501 and DQB1*0301 seemed to have a further increased risk of developing AA compared to individuals carrying only one of these HLA class II genes. Analysis of the combined presence of DQB1*0301 and DPA1*0103 in AA suggests......We investigated the DNA restriction polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DQA, -DQB, -DPA, and -DPB in 20 Danish patients with alopecia areata (AA) and in healthy Danes. The frequency in AA of the DQB1*0301 and DQw7 associated DQB Bgl/II 4.2 kb...... that an additive risk effect (synergism or interaction) exists between the DQB1*0301 and DPA1*0103 alleles which are situated at different HLA class II loci....

  13. HLA class II genes: typing by DNA analysis.

    Science.gov (United States)

    Bidwell, J L; Bidwell, E A; Bradley, B A

    1990-04-01

    A detailed understanding of the structure and function of the human major histocompatibility complex (MHC) has ensued from studies by molecular biologist during the last decade. Virtually all of the HLA genes have now been cloned, and the nucleotide sequences of their different allelic forms have been determined. Typing for these HLA alleles is a fundamental prerequisite for tissue matching in allogeneic organ transplantation. Until very recently, typing procedures have been dominated by serological and cellular methods. The availability of cloned DNA from HLA genes has now permitted the technique of restriction fragment length polymorphism (RFLP) analysis to be applied, with remarkable success and advantage, to phenotyping of both HLA Class I and Class II determinants. For the HLA Class II genes DR and DQ, a simple two-stage RFLP analysis permits the accurate identification of all specificities defined by serology, and of many which are defined by cellular typing. At the present time, however, RFLP typing of HLA Class I genes is not as practicable or as informative as that for HLA Class II genes. The present clinical applications of HLA-DR and DQ RFLP typing are predominantly in phenotyping of living donors, including selection of HLA-matched volunteer bone marrow donors, in allograft survival studies, and in studies of HLA Class II-associated diseases. However, the time taken to perform RFLP analysis precludes its use for the typing of cadaveric kidney donors. Nucleotide sequence data for the alleles of HLA Class II genes have now permitted the development of allele-specific oligonucleotide (ASO) typing, a second category of DNA analysis. This has been greatly facilitated by the ability to amplify specific HLA Class II DNA 'target' sequences using the polymerase chain reaction (PCR) technique. The accuracy of DNA typing techniques should ensure that this methodology will eventually replace conventional HLA phenotyping.

  14. In silico designing breast cancer peptide vaccine for binding to MHC class I and II: A molecular docking study.

    Science.gov (United States)

    Mahdavi, Manijeh; Moreau, Violaine

    2016-12-01

    Antigenic peptides or cancer peptide vaccines can be directly delivered to cancer patients to produce immunologic responses against cancer cells. Specifically, designed peptides can associate with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells activating anti-tumor effector mechanisms by triggering helper T cell (Th) or cytotoxic T cells (CTL). In general, high binding to MHCs approximately correlates with in vivo immunogenicity. Consequently, a molecular docking technique was run on a library of novel discontinuous peptides predicted by PEPOP from Human epidermal growth factor receptor 2 (HER2 ECD) subdomain III. This technique is expected to improve the prediction accuracy in order to identify the best MHC class I and II binder peptides. Molecular docking analysis through GOLD identified the peptide 1412 as the best MHC binder peptide to both MHC class I and II molecules used in the study. The GOLD results predicted HLA-DR4, HLA-DP2 and TCR as the most often targeted receptors by the peptide 1412. These findings, based on bioinformatics analyses, can be exploited in further experimental analyses in vaccine design and cancer therapy to find possible proper approaches providing beneficial effects.

  15. Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major

    DEFF Research Database (Denmark)

    ElHassan, A M; Gaafar, A; Theander, T G

    1995-01-01

    , identified morphologically and by their expression of specific cell markers, included Langerhans cells, macrophages, follicular dendritic cells, and interdigitating reticulum cells of the paracortex of lymph nodes. These cells expressed MHC class II antigens and contained Leishmania antigen. Since some...

  16. IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments

    Directory of Open Access Journals (Sweden)

    Vardjan Nina

    2012-06-01

    Full Text Available Abstract Background In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ can express major histocompatibility complex (MHC class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT astrocytes and in astrocytes devoid of IFs. Methods The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor546-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software. Results Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor546-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-γ-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-γ-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent. Conclusions Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a

  17. Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

    Science.gov (United States)

    Minias, Piotr; Bateson, Zachary W; Whittingham, Linda A; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O

    2016-01-01

    Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

  18. Direct activation of human dendritic cells by particle-bound but not soluble MHC class II ligand.

    Directory of Open Access Journals (Sweden)

    Renato B Baleeiro

    Full Text Available Dendritic cells (DCs are key activators of cellular immune responses through their capacity to induce naïve T cells and sustained effector T cell responses. This capacity is a function of their superior efficiency of antigen presentation via MHC class I and class II molecules, and the expression of co-stimulatory cell surface molecules and cytokines. Maturation of DCs is induced by microbial factors via pattern recognition receptors such as Toll-like receptors, pro-inflammatory cytokines or cognate interaction with CD4(+ T cells. Here we show that, unexpectedly, the PanDR helper T cell epitope PADRE, a generic T helper cell antigen presented by a large fraction of HLA-DR alleles, when delivered in particle-bound form induced maturation of human DCs. The DCs that received the particle-bound PADRE displayed all features of fully mature DCs, such as high expression of the co-stimulatory molecules CD80, CD86, CD83, the MHC-II molecule HLA-DR, secretion of high levels of the biologically active IL-12 (IL-12p70 and induction of vigorous proliferation of naïve CD4(+ T cells. Furthermore, the maturation of DCs induced by particle-bound PADRE was shown to involve sphingosine kinase, calcium signaling from internal sources and downstream signaling through the MAP kinase and the p72syk pathways, and finally activation of the transcription factor NF-κB. Based on our findings, we propose that particle-bound PADRE may be used as a DC activator in DC-based vaccines.

  19. Class II malocclusion therapy using fixed orthodontic appliance

    Directory of Open Access Journals (Sweden)

    Škufca Bojan

    2007-01-01

    Full Text Available Background. Depending on the indication, and the age of a patient, class II division I malocclusion can be treated by a fixed or mobile orthodontic appliance, with or without teeth extraction. Case report. A treatment of a male patient, 15 years old, with dentoalveolar class II division I was described. On the base of clinical findings, study case analysis, analysis of orthopan and profile cephalogram, there were class II division I with protrusion of frontal teeth and mild crowding in lower jaw assessed. The patient was treated by fixed orthodontics appliances (SWA Roth .022" in both jaws for 18 months, with the retention period of the same length. Conclusion. Fixed ortodontic appliances are necessary when bodily movement of the teeth is indicated - in this case for cuspids distalization and retraction of incisors.

  20. Liposome-coupled antigens are internalized by antigen-presenting cells via pinocytosis and cross-presented to CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Yuriko Tanaka

    Full Text Available We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs to CD8+ T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8+ T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8+ T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8+ T cells. Thus, these liposome-coupled antigens

  1. Class II malocclusion nonextraction treatment with growth control

    Directory of Open Access Journals (Sweden)

    Zilda Lúcia Valentim Assunção

    2014-12-01

    Full Text Available The present study reports a case of Angle Class II malocclusion treatment of a male growing patient with 10-mm overjet, excessive overbite and transverse maxillary deficiency. The case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO, with DI equal to or greater than 10, as a requirement for the title of certified by the BBO.

  2. Role of antigen presentation in the production of pro-inflammatory cytokines in obese adipose tissue.

    Science.gov (United States)

    Majdoubi, Abdelilah; Kishta, Osama A; Thibodeau, Jacques

    2016-06-01

    Type II diabetes regroups different physiological anomalies that ultimately lead to low-grade chronic inflammation, insulin resistance and loss of pancreatic β-cells. Obesity is one of the best examples of such a condition that can develop into Metabolic Syndrome, causing serious health problems of great socio-economic consequences. The pathological outcome of obesity has a genetic basis and depends on the delicate balance between pro- and anti-inflammatory effectors of the immune system. The causal link between obesity and inflammation is well established. While innate immunity plays a key role in the development of a pro-inflammatory state in obese adipose tissues, it has now become clear that adaptive immune cells are also involved and participate in the cascade of events that lead to metabolic perturbations. The efficacy of some immunotherapeutic protocols in reducing the symptoms of obesity-driven metabolic syndrome in mice implicated all arms of the immune response. Recently, the production of pathogenic immunoglobulins and pro-inflammatory cytokines by B and T lymphocytes suggested an auto-immune basis for the establishment of a non-healthy obese state. Understanding the cellular landscape of obese adipose tissues and how immune cells sustain chronic inflammation holds the key to the development of targeted therapies. In this review, we emphasize the role of antigen-presenting cells and MHC molecules in obese adipose tissue and the general contribution of the adaptive arm of the immune system in inflammation-induced insulin resistance.

  3. Treatment of Class II Division 1 Malocclusion using Cervical Headgear

    Directory of Open Access Journals (Sweden)

    Priska Lestari Hendrawan

    2013-07-01

    Full Text Available Class II division 1 malocclusions have many variation and treatment options. Choosing the right treatment begins with a correct diagnosis. The aim of this article is to describe treatment of Class II division 1 malocclusion in a growing patient using combined cervical headgear and non-extraction fixed orthodontic therapy. Class I molar and canine relationship was achieved with normal overbite and overjet. There is improvement in jaw relationship and facial profile. This correction was achieved by downward displacement and inhibition of the forward growth of maxilla with favorable growth of mandible, upper molar distalization and retraction of upper incisors from cervical headgear use. There was neither downward rotation of the mandible nor maxillary first molar extrusion. Treatment time, favorable mandibular growth pattern and patient compliance proved to be determining factors in the success of this treatment.DOI: 10.14693/jdi.v16i3.106

  4. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.

    Science.gov (United States)

    Srivastava, Smita; Grace, Patricia S; Ernst, Joel D

    2016-01-13

    Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion.

  5. Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles

    OpenAIRE

    Fujita, Yoshio; Taguchi, Hiroaki

    2011-01-01

    Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens), carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1) the addition of f...

  6. Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Worning, Peder;

    2004-01-01

    to the MHC class II complex HLA-DR4(B1*0401). Prior identification of information-rich (anchor) positions in the binding motif is shown to improve the predictive performance of the Gibbs sampler. Similarly, a consensus solution obtained from an ensemble average over suboptimal solutions is shown...

  7. Evaluation of mandibular length in subjects with Class I and Class II skeletal patterns using the cervical vertebrae maturation

    OpenAIRE

    Rodrigo Generoso; Elaine Cristina Sadoco; Mônica Costa Armond; Gustavo Hauber Gameiro

    2010-01-01

    The aim of this study was to compare the mandibular size in boys and girls with Class I and Class II skeletal patterns, taking into consideration the bone maturation stage, as defined by the cervical vertebrae maturation. One hundred and sixty cephalometric radiographs were obtained from subjects (aged between 7 and 12 years) with Class I or Class II skeletal patterns, according to the ANB angle and WITS appraisal. The Class I sample consisted of 80 subjects (40 boys, 40 girls). The Class II ...

  8. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method

    Directory of Open Access Journals (Sweden)

    Lund Ole

    2007-07-01

    Full Text Available Abstract Background Antigen presenting cells (APCs sample the extra cellular space and present peptides from here to T helper cells, which can be activated if the peptides are of foreign origin. The peptides are presented on the surface of the cells in complex with major histocompatibility class II (MHC II molecules. Identification of peptides that bind MHC II molecules is thus a key step in rational vaccine design and developing methods for accurate prediction of the peptide:MHC interactions play a central role in epitope discovery. The MHC class II binding groove is open at both ends making the correct alignment of a peptide in the binding groove a crucial part of identifying the core of an MHC class II binding motif. Here, we present a novel stabilization matrix alignment method, SMM-align, that allows for direct prediction of peptide:MHC binding affinities. The predictive performance of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC and three mouse H2-IA alleles. Results The predictive performance of the SMM-align method was demonstrated to be superior to that of the Gibbs sampler, TEPITOPE, SVRMHC, and MHCpred methods. Cross validation between peptide data set obtained from different sources demonstrated that direct incorporation of peptide length potentially results in over-fitting of the binding prediction method. Focusing on amino terminal peptide flanking residues (PFR, we demonstrate a consistent gain in predictive performance by favoring binding registers with a minimum PFR length of two amino acids. Visualizing the binding motif as obtained by the SMM-align and TEPITOPE methods highlights a series of fundamental discrepancies between the two predicted motifs. For the DRB1*1302 allele for instance, the TEPITOPE method favors basic amino acids at most anchor positions, whereas the SMM-align method identifies a preference for hydrophobic or neutral amino acids at the anchors. Conclusion

  9. Angle Class II malocclusion treated with extraction of permanent teeth.

    Science.gov (United States)

    Barreto, Gustavo Mattos

    2013-01-01

    Angle Class II malocclusion associated with anterior open bite in adult patients demands a carefully elaborated orthodontic planning, aiming at restoring not only harmonious dental and facial esthetics, but also a balanced masticatory function. Orthognathic surgery or permanent teeth extraction are often the choice of treatment, therefore, treatment decision is related to all dental, skeletal and functional aspects. The present report discusses orthodontic compensation carried out by means of upper premolar extraction performed to correct the Class II canine relationship and, consequently, the anterior open bite, accepting that the upper incisors be retroclined. This clinical case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as part of the requirements for obtaining the BBO Certification.

  10. Angle Class II malocclusion treated with extraction of permanent teeth

    Directory of Open Access Journals (Sweden)

    Gustavo Mattos Barreto

    2013-08-01

    Full Text Available Angle Class II malocclusion associated with anterior open bite in adult patients demands a carefully elaborated orthodontic planning, aiming at restoring not only harmonious dental and facial esthetics, but also a balanced masticatory function. Orthognathic surgery or permanent teeth extraction are often the choice of treatment, therefore, treatment decision is related to all dental, skeletal and functional aspects. The present report discusses orthodontic compensation carried out by means of upper premolar extraction performed to correct the Class II canine relationship and, consequently, the anterior open bite, accepting that the upper incisors be retroclined. This clinical case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as part of the requirements for obtaining the BBO Certification.

  11. Multiple regenerative techniques for class II furcation defect

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2012-01-01

    Full Text Available Regeneration of the periodontium is a major goal in the treatment of teeth affected by periodontitis. Periodontal regeneration is quite challenging, especially when it is in the furcation area. There are several techniques used alone or in combination, considered to achieve periodontal regeneration, including bone grafts or substitutes, guided tissue regeneration, root surface modification, and biological mediators. Many factors may account for variability in the response to regenerative therapy in class II furcation. This case report describes the management of a buccal class II furcation defect, with the help of surgical intervention, including the guided tissue regeneration (GTR membrane and bone graft materials. This combined treatment resulted in a healthy periodontium, with radiographic evidence of alveolar bone gain. This case report demonstrates that proper diagnosis, followed by removal of the etiological factors and utilizing combined treatment modalities, restored health and function of the tooth with severe attachment loss, at the 18-month follow-up.

  12. Relation between Angle Class II malocclusion and deleterious oral habits

    Directory of Open Access Journals (Sweden)

    José Tarcísio Lima Ferreira

    2012-12-01

    Full Text Available INTRODUCTION: Oral habits may interfere on the growth and development of the stomatognathic system and orofacial myofunctional conditions, producing changes in the position of teeth in their dental arches. OBJECTIVE: The purpose of this study was to verify the presence of deleterious oral habits in individuals with malocclusion and see if there is a predominance of Class II malocclusion in these individuals. METHODS: The records of 140 patients treated at the Clinic of Preventive Orthodontics FORP-USP who had already completed treatment were randomly selected and analyzed. Their ages ranged from 6 to 10 years and 11 months. Associations were made between the presence or absence of deleterious oral habits, type and number of habits found in each individual and the type of malocclusion according to Angle classification. The statistical analysis used was the Chi-square test with a significance level of 5%. History of deleterious oral habits was found in 67.1% of individuals. RESULTS: The Class I malocclusion was most frequent (82.9%, followed by Class II malocclusion (12.1% and Class III (5%. CONCLUSION: There was a predominance of Class II malocclusion in individuals with a history of deleterious oral habits.INTRODUÇÃO: hábitos bucais podem interferir no crescimento e desenvolvimento do sistema estomatognático e nas condições miofuncionais bucofaciais, acarretando alterações no posicionamento dos dentes nas respectivas arcadas dentárias. OBJETIVO: o objetivo dessa pesquisa foi verificar a presença de hábitos bucais deletérios em indivíduos portadores de má oclusão e observar se existe predominância de má oclusão Classe II de Angle nesses indivíduos. MÉTODOS: foram selecionadas, aleatoriamente, e analisadas 140 fichas de pacientes atendidos na Clínica de Ortodontia Preventiva da FORP-USP, que já haviam recebido alta no tratamento. A faixa etária variou dos 6 anos a 10 anos e 11 meses. Foram realizadas associações entre

  13. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells.

    Science.gov (United States)

    Matsuzaki, Junko; Tsuji, Takemasa; Luescher, Immanuel; Old, Lloyd J; Shrikant, Protul; Gnjatic, Sacha; Odunsi, Kunle

    2014-04-01

    Tumor antigen-specific CD4(+) T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4(+) T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157-170 peptide vaccination in patients with ovarian cancer. Although both subsets recognized exogenous NY-ESO-1 protein pulsed on DP04(+) target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4(+) T cells more efficiently recognized the short 8-9-mer peptides than the non-tumor-recognizing CD4(+) T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways, such as the proteasomal degradation and transporter-associated with antigen-processing-mediated peptide transport, were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacologic inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrate that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple nonclassical antigen-processing pathways. Harnessing the direct tumor-recognizing ability of CD4(+) T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment.

  14. Cylindrical bubbles and blobs from a Class II Hydrophobin

    Science.gov (United States)

    Russo, Paul; Pham, Michael; Blalock, Brad

    2012-02-01

    Cerato ulmin is a class II hydrophobin. In aqueous suspensions, it easily forms cylindrical air bubbles and cylindrical oil blobs. The conditions for formation of these unusual structures will be discussed, along with scattering and microscopic investigations of their remarkable stability. Possible applications in diverse fields including polymer synthesis and oil spill remediation will be considered. Acknowledgment is made to Dr. Wayne C. Richards of the Canadian Forest Service for the gift of Cerato ulmin.

  15. Characterization of recombination in the HLA class II region

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, M.; Carrington, M. [National Cancer Institute, Frederick, MD (United States); Noble, J. [Roche Molecular Systems, Almeda, CA (United States)] [and others

    1997-02-01

    Studies of linkage disequilibrium across the HLA class II region have been useful in predicting where recombination is most likely to occur. The strong associations between genes within the 85-kb region from DQB1 to DRB1 are consistent with low frequency of recombination in this segment of DNA. Conversely, a lack of association between alleles of TAP1 and TAP2 ({approximately}15 kb) has been observed, suggesting that recombination occurs here with relatively high frequency. Much of the HLA class II region has now been sequenced, providing the tools to undertake detailed analysis of recombination. Twenty-seven families containing one or two recombinant chromosomes within the 500-kb interval between the DPB1 and DRB1 genes were used to determine patterns of recombination across this region. SSCP analysis and microsatellite typing yielded identification of 127 novel polymorphic markers distributed throughout the class II region, allowing refinement of the site of crossover in 30 class II recombinant chromosomes. The three regions where recombination was observed most frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11 cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further characterization, pending identification of additional informative markers, while four recombinants were localized to other intervals (outliers). Analysis of association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no linkage disequilibrium, supporting the familial recombination data. A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA){sub 12} tandem repeat within the TAP2 gene. 74 refs., 3 figs., 2 tabs.

  16. [Routine application of HLA class II oligotyping. Value of automatization].

    Science.gov (United States)

    Caillat-Zucman, S; Bach, J F

    1992-12-02

    HLA class II typing by DNA amplification and hybridization with allele-specific oligonucleotides has led to an improvement of the overall typing accuracy. In an attempt to apply this procedure to a large-scale analysis, we sought to implement an automation system using the Biomek 1,000 robotic work-station. This system allows a rapid preparation of many consecutive samples and avoids the risk of human errors. It is now routinely used in several laboratories.

  17. Treatment of a Class II deepbite with microimplant anchorage.

    Science.gov (United States)

    Park, Hyo-Sang; Kim, Ji-Yeun; Kwon, Tae-Geon

    2011-03-01

    The goal of this report was to illustrate new treatment mechanics for using microimplants for the treatment of a Class II Division 2 deepbite malocclusion. A 29-year-old woman with a deepbite was treated with the aid of microimplant anchorage. Microimplants placed between the maxillary second premolars and first molars were used as anchorage to apply a distal force to the anterior teeth to correct the Class II canine and molar relationships. A distal force was applied to long hooks that were crimped between the lateral incisors and the canines. By applying a backward force to the long hooks, the maxillary anterior teeth experienced palatal root movement with no change in the vertical and anteroposterior positions of the incisal edges. The distal extrusive movement of the maxillary second molars achieved by disengaging the second molars from the archwire during distal force application and an anterior bite-block bonded on the lingual surface of the maxillary central incisors produced the increase in vertical dimension. The distal force to the long extended hooks from the microimplants was possibly good mechanics for obtaining the palatal root movement and correcting the Class II canine and molar relationships. The anterior bite-block and disengagement of the maxillary second molars during distal force application were effective for increasing the vertical dimension.

  18. MHC Class II haplotypes of Colombian Amerindian tribes.

    Science.gov (United States)

    Yunis, Juan J; Yunis, Edmond J; Yunis, Emilio

    2013-07-01

    We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family), Embera, Waunana (Choco linguistic family), Puinave and Nukak (Maku-Puinave linguistic families), Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family), Guahibo and Guayabero (Guayabero Linguistic Family), Curripaco and Piapoco (Arawak linguistic family) and Yucpa (Karib linguistic family). for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1). Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America.

  19. MHC Class II haplotypes of Colombian Amerindian tribes

    Directory of Open Access Journals (Sweden)

    Juan J. Yunis

    2013-01-01

    Full Text Available We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family, Embera, Waunana (Choco linguistic family, Puinave and Nukak (Maku-Puinave linguistic families, Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family, Guahibo and Guayabero (Guayabero Linguistic Family, Curripaco and Piapoco (Arawak linguistic family and Yucpa (Karib linguistic family. for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1. Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America.

  20. CD4 binding to major histocompatibility complex class II antigens induces LFA-1-dependent and -independent homotypic adhesion of B lymphocytes.

    Science.gov (United States)

    Kansas, G S; Cambier, J C; Tedder, T F

    1992-01-01

    T helper cells recognize processed antigen (Ag) in the context of major histocompatibility complex (MHC) class II antigens present on the surface of B cells and other Ag-presenting cells. This interaction is mediated through the T cell receptor complex with associate recognition of class II molecules by the CD4 molecule. In this study, the binding of a soluble recombinant CD4/Ig heavy chain fusion protein (CD4-gamma 3) or monoclonal antibody (mAb) to class II antigens on human B cells was shown to induce rapid and specific homotypic adhesion of B cells and most B lymphoblastoid cell lines. mAb reactive with CD4 inhibited CD4-gamma 3-induced adhesion and a mutant B lymphoblastoid cell line deficient in class II antigens failed to respond. Induction of homotypic adhesion was dependent on energy metabolism and a functional cytoskeleton, and class II+ pre-B cells did not exhibit adhesion in response to these stimuli, suggesting that cross-linking of class II molecules generated a transmembrane signal and did not simply aggregate cells. In addition, MHC class II-induced adhesion was Fc receptor independent, as 15 mAb of different Ig isotypes reactive with HLA-D or HLA-DQ gene products induced adhesion. Anti-class II mAb and CD4-gamma 3 were able to induce adhesion at concentrations as low as 10 ng/ml and 100 ng/ml, respectively. Suboptimal stimulation of B cell lines through HLA-D antigens induced homotypic adhesion that was dependent on the activation of LFA-1 (CD11a/CD18), and which could be blocked by specific mAb. However, at greater signal strengths, adhesion was not blocked by mAb against the known adhesion receptors, suggesting the induction of a novel adhesion pathway. Consistent with this, homotypic adhesion induced by engagement of MHC class II antigens was observed with LFA-1-deficient B cell lines, and was independent of CD49d or CD18 expression. Thus, the direct engagement of B cell class II antigens by CD4 is likely to generate transmembrane signals which

  1. Evolução dos preparos das cavidades de classe II Developments in preparation of class II cavities

    Directory of Open Access Journals (Sweden)

    Mary Miyuki ONO

    1997-01-01

    Full Text Available A evolução dos preparos de classe II com a introdução de novos materiais e a conscientização da importância da preservação de estrutura dental sadia são abordadas nos preparos do tipo Almqvist, Roggenkamp e túnel, em que se observa a necessidade de menor desgaste da estrutura dentária, com aumento da resistência à fratura, melhor estética e melhor retençãoDevelopments in preparation of class II cavities with the introduction of new materials and awareness of the importance of preservation of a sound dental structure are broached in preparations of the type Almqvist, Roggenkamp and tunnel, where the need for less wear of the dental structure was observed with an increase in fracture strength, better aesthetics, and better retention

  2. Spectral energy distribution analysis of class I and class II FU Orionis stars

    Energy Technology Data Exchange (ETDEWEB)

    Gramajo, Luciana V.; Gómez, Mercedes [Observatorio Astronómico, Universidad Nacional de Córdoba, Argentina, Laprida 854, 5000 Córdoba (Argentina); Rodón, Javier A., E-mail: luciana@oac.uncor.edu, E-mail: mercedes@oac.uncor.edu, E-mail: jrodon@eso.org [European Southern Observatory, Alonso de Córdova 3107, Vitacura, Casilla 19001, Santiago 19 (Chile)

    2014-06-01

    FU Orionis stars (FUors) are eruptive pre-main sequence objects thought to represent quasi-periodic or recurring stages of enhanced accretion during the low-mass star-forming process. We characterize the sample of known and candidate FUors in a homogeneous and consistent way, deriving stellar and circumstellar parameters for each object. We emphasize the analysis in those parameters that are supposed to vary during the FUor stage. We modeled the spectral energy distributions of 24 of the 26 currently known FUors, using the radiative transfer code of Whitney et al. We compare our models with those obtained by Robitaille et al. for Taurus class II and I sources in quiescence periods by calculating the cumulative distribution of the different parameters. FUors have more massive disks: we find that ∼80% of the disks in FUors are more massive than any Taurus class II and I sources in the sample. Median values for the disk mass accretion rates are ∼10{sup –7} M {sub ☉} yr{sup –1} versus ∼10{sup –5} M {sub ☉} yr{sup –1} for standard young stellar objects (YSOs) and FUors, respectively. While the distributions of envelope mass accretion rates for class I FUors and standard class I objects are similar, FUors, on average, have higher envelope mass accretion rates than standard class II and class I sources. Most FUors (∼70%) have envelope mass accretion rates above 10{sup –7} M {sub ☉} yr{sup –1}. In contrast, 60% of the classical YSO sample has an accretion rate below this value. Our results support the current scenario in which changes experimented by the circumstellar disk explain the observed properties of these stars. However, the increase in the disk mass accretion rate is smaller than theoretically predicted, although in good agreement with previous determinations.

  3. Human Leukocyte Antigen Class II Alleles Are Associated with Hepatitis C Virus Natural Susceptibility in the Chinese Population

    Directory of Open Access Journals (Sweden)

    Ming Yue

    2015-07-01

    Full Text Available Human leukocyte antigen (HLA class II molecule influences host antigen presentation and anti-viral immune response. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs within HLA class II gene were associated with different clinical outcomes of hepatitis C virus (HCV infection. Three HLA class II SNPs (rs3077, rs2395309 and rs2856718 were genotyped by TaqMan assay among Chinese population, including 350 persistent HCV infection patients, 194 spontaneous viral clearance subjects and 973 HCV-uninfected control subjects. After logistic regression analysis, the results indicated that the rs2856718 TC genotype was significantly associated with the protective effect of the HCV natural susceptibility (adjusted OR: 0.712, 95% CI: 0.554–0.914 when compared with reference TT genotype, and this remained significant after false discovery rate (FDR correction (p = 0.024. Moreover, the protective effect of rs2856718 was observed in dominant genetic models (adjusted OR: 0.726, 95% CI: 0.574–0.920, and this remained significant after FDR correction (p = 0.024. In stratified analysis, a significant decreased risk was found in rs2856718C allele in the male subgroup (adjusted OR: 0.778, 95% CI: 0.627–0.966 and hemodialysis subgroup (adjusted OR: 0.713, 95% CI: 0.552–0.921. Our results indicated that the genetic variations of rs2856718 within the HLA-DQ gene are associated with the natural susceptibility to HCV infection among the Chinese population.

  4. The shape and size of the sella turcica in skeletal Class I, Class II, and Class III Saudi subjects.

    Science.gov (United States)

    Alkofide, Eman A

    2007-10-01

    The purpose of this study was to describe the shape and measure the size of the sella turcica in Saudi subjects with different skeletal types. Lateral cephalometric radiographs of 180 individuals (90 males and 90 females) with an age range of 11-26 years were taken and distributed according to skeletal classification; 60 Class I, 60 Class II, and 60 Class III. The sella turcica on each radiograph was analysed and measured to determine the shape of the sella, in addition to the linear dimensions of length, depth, and diameter. A Student's t-test was used to calculate differences in linear dimensions, while a one-way analysis of variance was performed to study the relationship between skeletal type and sella size. The results show that the sella turcica presented with a normal morphology in the majority of subjects (67 per cent). No significant differences in linear dimensions between genders could be found. When age was evaluated, significant differences were found between the older (15 years or more) and the younger (11-14 years) age groups at the 0.01 and 0.001 levels for length, depth, and diameter. Sella size of the older age group was larger than in the younger age group. When skeletal type was compared with sella size, a significant difference was found in the diameter of sella between the Class II and Class III subjects (P sella turcica area in Saudi subjects.

  5. 78 FR 14013 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Wheelchair Elevator

    Science.gov (United States)

    2013-03-04

    ... Notification; Class II Devices; Wheelchair Elevator AGENCY: Food and Drug Administration, HHS. ACTION: Final... requesting exemption from premarket notification requirements for wheelchair elevator devices commonly known... another, usually in a wheelchair. This order exempts wheelchair elevators, class II devices,...

  6. Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles

    Directory of Open Access Journals (Sweden)

    Taguchi Hiroaki

    2011-08-01

    Full Text Available Abstract Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens, carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1 the addition of functional components, e.g., T-cell epitopes, cell-penetrating peptides, and lipophilic moieties; and (2 synthetic approaches using size-defined nanomaterials, e.g., self-assembling peptides, non-peptidic dendrimers, and gold nanoparticles, as antigen-displaying platforms. This review summarizes the recent experimental studies directed to the development of multiple antigen-presenting peptide vaccine systems.

  7. Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

    Directory of Open Access Journals (Sweden)

    Cleo Goyvaerts

    2015-01-01

    Full Text Available In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

  8. Signal transduction by HLA class II antigens expressed on activated T cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Martin, P J; Schieven, G L;

    1991-01-01

    Human T cells express HLA class II antigens upon activation. Although activated, class II+ T cells can present alloantigens under certain circumstances, the functional role of class II antigens on activated T cells remains largely unknown. Here, we report that cross-linking of HLA-DR molecules ex...

  9. MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

    Directory of Open Access Journals (Sweden)

    Judith A. James

    2012-12-01

    Full Text Available Anthrax Lethal Toxin consists of Protective Antigen (PA and Lethal Factor (LF, and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class II versus non-MHC class II genes in the humoral response to PA and LF immunization using three immunized strains of inbred mice: A/J (H-2k at the MHC class II locus, B6 (H-2b, and B6.H2k (H-2k. IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by the non-MHC class II genetic background. Conversely, the humoral fine specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes, while the specificity of reactivity to PA was more dependent on MHC class II. Common epitopes, reactive in all strains, occurred in both LF and PA responses. These results demonstrate that MHC class II differentially influences humoral immune responses to LF and PA.

  10. Evaluation depth of the curve of Spee in class I, class II, and class III malocclusion: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar

    2015-01-01

    Full Text Available Occlusal plane is an essential consideration when multiple long-span posterior restorations are designed. When restorations are added to an existing tooth arrangement characterized by rotated, tipped, or extruded teeth, excursive interferences may be incorporated, resulting in detrimental squeal. The curve of Spee, which exists in the ideal natural dentition, allows harmony to exist between the anterior tooth and condylar guidance. This curve exists in the sagittal plane and is the best viewed from a lateral aspect. It permits total posterior disclusion on mandibular protrusion, given proper anterior tooth guidance. It is unclear that whether the curve of Spee is a description of the occlusal surface of each arch separately or in maximal intercuspation. The purpose of this study was to examine the differences in the depth of curve of Spee between the class I, class II, class III and to investigate the relationship of depth of curve of Spee with over jet, over-bite.

  11. Simultaneous observation of water and class I methanol masers toward class II methanol maser sources

    CERN Document Server

    Kang, Hyunwoo; Byun, Do-Young; Lee, Seokho; Park, Yong-Sun

    2015-01-01

    We present a simultaneous single-dish survey of 22 GHz water maser and 44 GHz and 95 GHz class I methanol masers toward 77 6.7 GHz class II methanol maser sources, which were selected from the Arecibo methanol maser Galactic plane survey (AMGPS) catalog.Water maser emission is detected in 39 (51%) sources, of which 15 are new detections. Methanol maser emission at 44 GHz and 95 GHz is found in 25 (32%) and 19 (25%) sources, of which 21 and 13 sources are newly detected, respectively. We find 4 high-velocity (> 30 km/s) water maser sources, including 3 dominant blue- or redshifted outflows.The 95 GHz masers always appear with the 44 GHz maser emission. They are strongly correlated with 44 GHz masers in velocity, flux density, and luminosity, while they are not correlated with either water or 6.7 GHz class II methanol masers. The average peak flux density ratio of 95 GHz to 44 GHz masers is close to unity, which is two times higher than previous estimates. The flux densities of class I methanol masers are more ...

  12. HLA class I and class II associations with ESRD in Saudi Arabian population.

    Directory of Open Access Journals (Sweden)

    Nuha Mahmoud Hamdi

    Full Text Available BACKGROUND: Chronic renal failure (CRF leads in the majority of instances to end stage renal disease (ESRD requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population. METHODOLOGY: A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated control. Patients and control groups were typed by SSOP lumenix techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18, B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30-DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50, A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02, A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective haplotypes. CONCLUSION: The high Relative Risk (RR observed and its statistical correlation reflect the strength of the described association between HLA antigens and ESRD.

  13. Modulation of T cell responses after cross-talk between antigen presenting cells and T cells: a give-and-take relationship.

    Science.gov (United States)

    Wauben, Marca H M; 't Hoen, Esther N M; Taams, Leonie S

    2003-01-01

    T cells presenting antigens in the context of MHC class II can induce anergy. In rat CD4+ T cell clones we have shown that depending on the depth of anergy other T cell responses can be inhibited in the presence of professional antigen presenting cells (APCs). This inhibition is cell-contact dependent, and APCs recovered from co-cultures with suppressive anergic T cells are modulated in their capacity to activate T cells. No changes in cell surface expression of MHC molecules, B7-1/B7-2, and OX40L were detected. Remarkably cell clusters formed by anergic T cells appeared to be more tight than clusters of activated T cells, and after fluorescent cell surface labelling of T cells, transfer of label was more profound in co-cultures of anergic T cells and APCs compared to activated T cells and APCs. Previously, it has been shown that activated T cells can absorb molecules from APCs in a unidirectional process. We now have evidence that also APCs can absorb cell surface molecules from T cells during APC-T cell co-cultures. We speculate that the quantity and quality of molecule reshuffling during cross-talk between T cells and APCs play a role in the regulation of the T cell response.

  14. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells

    NARCIS (Netherlands)

    Eggermont, L.J.; Paulis, L.E.M.; Tel, J.; Figdor, C.G.

    2014-01-01

    Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artif

  15. Characterization and expression of MHC class II alpha and II beta genes in mangrove red snapper (Lutjanus argentimaculatus).

    Science.gov (United States)

    Wang, Tianyan; Tan, Shangjin; Cai, Zhonghua

    2015-12-01

    The major histocompatibility complex (MHC) class II plays a key role in adaptive immunity by presenting foreign peptides to CD4(+) T cells and by triggering the adaptive immune response. While the structure and function of MHC class II have been well characterized in mammalian, limited research has been done on fishes. In this study, we characterized the gene structure and expression of MHC class II α (Lunar-DAA) and II β (Lunar-DAB) of mangrove red snapper (Lutjanus argentimaculatus). Both genes shared, respectively, a high similarity and typical features with other vertebrate MHC class II α and II β. The phylogenetic analysis of the deduced peptides revealed that both Lunar-DAA and Lunar-DAB were located in the teleost subclass. Western blotting analyses indicated that both MHC class II α and II β were expressed ubiquitously in immune-related cells, tissues and organs, and that MHC class II α and II β chains existed mainly as heterodimers. While it was highly expressed in gills, thymus, head kidney (HK), spleen, head kidney macrophage and spleen leucocytes, MHC class II β chain was expressed with a low abundance in skin, intestine, stomach and heart. The highest expression of MHC class II β in thymus confirmed the conclusion that thymus is one of the primary lymphoid organs in fishes. The detection of MHC class II αβ dimers in HK macrophages and spleen leucocytes indicated that HK macrophages and spleen leucocytes play a critical role in the adaptive immunity in fishes. All these results provide valuable information for understanding the structure of MHC class II α and II β and their function in immune responses.

  16. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato

    2009-09-01

    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  17. Francisella tularensis elicits IL-10 via a PGE₂-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation.

    Directory of Open Access Journals (Sweden)

    Danielle Hunt

    Full Text Available Francisella tularensis is a bacterial pathogen that uses host-derived PGE₂ to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE₂ acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE₂ can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensismacrophage supernatant, which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 "resistant" class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE₂ can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE₂ drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE₂, these results suggest that a yet-to-be-identified PGE₂-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens.

  18. Regulation of NK-cell function by mucins via antigen-presenting cells.

    Science.gov (United States)

    Laskarin, G; Redzovic, A; Medancic, S Srsen; Rukavina, D

    2010-12-01

    Decidual antigen-presenting cells including dendritic cells (DCs) and CD14(+) macrophages, as mediators of the first encounter with fetal antigens, appear to be critically involved in the initiation of primary immune response by regulating innate- and adaptive immunity. Interleukin-15, produced by them, permits the proliferation and differentiation of CD3(-)CD16(-)CD94(+)NKG2A(+)CD56(+bright) decidual NK cells that identify trophoblast cells. These cells are able to kill them after Th1 cytokine overstimulation and by increasing the release of preformed cytotoxic mediators. Thus, the local microenvironment is a potent modulator of antigen-presenting cell functions. Tumor associated glycoprotein-72 (TAG-72) and mucine 1 (MUC-1) are glycoproteins secreted by uterine epithelial cells. Our hypothesis is that TAG-72 and MUC-1 are the natural ligands for carbohydrate recognition domains (CRDs) of endocytic mannose receptor (MR or CD206) and DC-specific ICAM non-integrin (DC-SIGN or CD209) expressed on decidual CD14(+) macrophages and CD1a(+) DCs. They might be able to condition antigen-presenting cells to produce distinct profiles of cyto/chemokines with consequential reduction in NK-cell numbers and cytotoxic potential leading to insufficient control over trophoblast growth. This hypothesis could explain the disappearance of MUC-1 beneath the attached embryo during the process of successful implantation when tight regulation of trophoblast invasion is needed. As IL-15 is the earliest and the most important factor in NK-cell proliferation, differentiation, and maturation, we expected primarily an increase of IL-15 expression in antigen-presenting cells concomitant with the disappearance of mucins and the enhancement in NK cells numbers and of cytotoxic potential after their close contact with early pregnancy decidual antigen-presenting cells. If our hypothesis is correct, it would contribute to the understanding of the role of mucins in the redirection of immune response

  19. A growth-related concept for skeletal class II treatment.

    Science.gov (United States)

    Teuscher, U

    1978-09-01

    The use of a combined activator--high-pull headgear appliance for treatment of Class II, Division 1 malocclusion is presented as a preliminary report. The activator itself is equipped with a palatal bar, lower lip pads, and torque-control auxiliaries for the upper incisors. The face-bow is mounted directly on the activator, and the extraoral force vector is equivalent to that of an anterior high-pull vector. During bite registration the veritcal displacement of the mandible is restricted to a minimum, and the anterior displacement should not exceed 6 mm. On the basis of current knowledge of the growth of the bony facial structures, treatment objectives and a specific approach for skeletal Class II correction are defined. Following these objectives, the therapy aims at correcting the malocclusion without diverting the anterior landmarks of the bony face from their specific lines of growth. This is brought about by the corresponding mechanics of the activator-headgear combination. The corrective effect of this appliance may be assumed to be the result of several different factors. The maxillary dentition is restrained in a posterior cranial direction, and an inhibitory effect on the maxilla counter to its line of development is attained. The mandibular dentition is influenced in an anterior downward direction by means of the bite registration, and the occlusion is unlocked during treatment. Any transfer of distally directed headgear forces from the maxilla to the mandible is prevented. Temporary stimulation of condylar growth, possibly combined with temporary posterior deflection of condylar growth, may also be induced. In this way it is possible to take maximum advantage of condylar growth in the sagittal dimension. Thus, not only is the malocclusion corrected but, at the same time, decisive profile improvement is achieved by anterior development of the mandible. From the experience gained so far with a Class II, Division 1 sample undergoing treatment with the

  20. Evaluation of mandibular length in subjects with Class I and Class II skeletal patterns using the cervical vertebrae maturation

    Directory of Open Access Journals (Sweden)

    Rodrigo Generoso

    2010-03-01

    Full Text Available The aim of this study was to compare the mandibular size in boys and girls with Class I and Class II skeletal patterns, taking into consideration the bone maturation stage, as defined by the cervical vertebrae maturation. One hundred and sixty cephalometric radiographs were obtained from subjects (aged between 7 and 12 years with Class I or Class II skeletal patterns, according to the ANB angle and WITS appraisal. The Class I sample consisted of 80 subjects (40 boys, 40 girls. The Class II sample also consisted of 80 subjects (40 boys, 40 girls. On a cross-sectional basis, mandibular length (Co-Gn was compared between groups and genders. The between-stages changes were also evaluated, with the cervical vertebrae analysis used for establishing the bone maturation stages at CS2, CS3, CS4 and CS5. The results were statistically analyzed by the Kruskal-Wallis test. The mandibular length differed between skeletal patterns only at the earlier stages of development. In the Class I pattern, the mandibular lengths of boys were greater than those of girls at stages CS2, CS4 and CS5, whereas in the Class II pattern, the mandibular lengths of boys were greater than those of girls at stages CS2, CS3 and CS4. The present results indicate a sexual dimorphism in the mandibular length at almost all stages of bone maturation, in exception of the CS5 stage in Class II.

  1. Comprehensive analysis of cooperative gene mutations between class I and class II in de novo acute myeloid leukemia.

    Science.gov (United States)

    Ishikawa, Yuichi; Kiyoi, Hitoshi; Tsujimura, Akane; Miyawaki, Shuichi; Miyazaki, Yasushi; Kuriyama, Kazutaka; Tomonaga, Masao; Naoe, Tomoki

    2009-08-01

    Acute myeloid leukemia (AML) has been thought to be the consequence of two broad complementation classes of mutations: class I and class II. However, overlap-mutations between them or within the same class and the position of TP53 mutation are not fully analyzed. We comprehensively analyzed the FLT3, cKIT, N-RAS, C/EBPA, AML1, MLL, NPM1, and TP53 mutations in 144 newly diagnosed de novo AML. We found 103 of 165 identified mutations were overlapped with other mutations, and most overlap-mutations consisted of class I and class II mutations. Although overlap-mutations within the same class were found in seven patients, five of them additionally had the other class mutation. These results suggest that most overlap-mutations within the same class might be the consequence of acquiring an additional mutation after the completion both of class I and class II mutations. However, mutated genes overlapped with the same class were limited in N-RAS, TP53, MLL-PTD, and NPM1, suggesting the possibility that these irregular overlap-mutations might cooperatively participate in the development of AML. Notably, TP53 mutation was overlapped with both class I and class II mutations, and associated with morphologic multilineage dysplasia and complex karyotype. The genotype consisting of complex karyotype and TP53 mutation was an unfavorable prognostic factor in entire AML patients, indicating this genotype generates a disease entity in de novo AML. These results collectively suggest that TP53 mutation might be a functionally distinguishable class of mutation.

  2. 40 CFR 147.3108 - Plugging Class I, II, and III wells.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Plugging Class I, II, and III wells... Certain Oklahoma Indian Tribes § 147.3108 Plugging Class I, II, and III wells. In addition to the... well: (a) For Class I and III wells: (1) The well shall be filled with mud from the bottom of the...

  3. How do CD4+ T cells detect and eliminate tumor cells that either lack or express MHC class II molecules?

    Directory of Open Access Journals (Sweden)

    Ole Audun Werner Haabeth

    2014-04-01

    Full Text Available CD4+ T cells contribute to tumor eradication, even in the absence of CD8+ T cells. Cytotoxic CD4+ T cells can directly kill MHC class II positive tumor cells. More surprisingly, CD4+ T cells can indirectly eliminate tumor cells that lack MHC class II expression. Here, we review the mechanisms of direct and indirect CD4+ T cell-mediated elimination of tumor cells. An emphasis is put on T cell receptor (TCR transgenic models, where anti-tumor responses of naïve CD4+ T cells of defined specificity can be tracked. Some generalizations can tentatively be made. For both MHCIIPOS and MHCIINEG tumors, presentation of tumor specific antigen by host antigen presenting cells (APCs appears to be required for CD4+ T cell priming. This has been extensively studied in a myeloma model (MOPC315, where host APCs in tumor-draining lymph nodes are primed with secreted tumor antigen. Upon antigen recognition, naïve CD4+ T cells differentiate into Th1 cells and migrate to the tumor. At the tumor site, the mechanisms for elimination of MHCIIPOS and MHCIINEG tumor cells differ. In a TCR transgenic B16 melanoma model, MHCIIPOS melanoma cells are directly killed by cytotoxic CD4+ T cells in a perforin/granzyme B-dependent manner. By contrast, MHCIINEG myeloma cells are killed by IFN-g stimulated M1-like macrophages. In summary, while the priming phase of CD4+ T cells appears similar for MHCIIPOS and MHCIINEG tumors, the killing mechanisms are different. Unresolved issues and directions for future research are addressed.

  4. SED analysis of class I and class II FU Orionis stars

    CERN Document Server

    Gramajo, Luciana V; Gómez, Mercedes

    2014-01-01

    FU Orionis stars (FUORS) are eruptive pre-main sequence objects thought to represent quasi-periodic or recurring stages of enhanced accretion during the low-mass star-forming process. We characterize the sample of known and candidate FUORS in an homogeneous and consistent way, deriving stellar and circumstellar parameters for each object. We emphasize the analysis in those parameters that are supposed to vary during the FUORS stage. We modeled the SEDs of 24 of the 26 currently known FUORS, using the radiative transfer code of Whitney et al (2003b). We compare our models with those obtained by Robitaille et al. (2007) for Taurus class II and I sources in quiescence periods, by calculating the cumulative distribution of the different parameters. FUORS have more massive disks: we find that $\\sim80\\%$ of the disks in FUORS are more massive than any Taurus class II and I sources in the sample. Median values for the disk mass accretion rates are ~ 1.e-7 Msun/yr vs ~ 1.e-5 Msun/yr for standard YSOs (young stellar o...

  5. Studying the Prevalence and Etiology of Class II Subdivision Malocclusion Utilizing Cone-Beam Computed Tomography

    Science.gov (United States)

    2013-04-24

    II SUBDIVISION MALOCCLUSION UTILIZING CONE-BEAM COMPUTED TOMOGRAPHY A THESIS Presented to the Faculty of the Uniform Services University of...K_Paper _Article _Book _ Poster _Presentation _Other 6. Title: ’Studying the Prevalence and Etiology of Class II Subdivision Malocclusion Utilizing...of any copyrighted material in the thesis manuscript entitled : ’STUDYING THE PREVALENCE AND ETIOLOGY OF CLASS II SUBDIVISION MALOCCLUSION

  6. 40 CFR 144.28 - Requirements for Class I, II, and III wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... annular pressure; (iii) The results from ground-water monitoring wells prescribed in paragraph (g)(1)(iii... drinking water and the well bore is prohibited. (2) The owner or operator of a Class I, II or III injection... water. (ii) For Class II wells: (A) The owner or operator shall not exceed a maximum injection...

  7. Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance

    Directory of Open Access Journals (Sweden)

    Lisa K. Denzin

    2013-12-01

    Full Text Available Major histocompatibility class II (MHCII molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs. This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM. DM activity is directly opposed by HLA-DO (DO, another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.

  8. Hyoid bone position and head posture comparison in skeletal Class I and Class II subjects: A retrospective cephalometric study

    Directory of Open Access Journals (Sweden)

    Pawankumar Dnyandeo Tekale

    2014-01-01

    Full Text Available Objective: The aim of the study was to investigate the hyoid bone position and the head posture using lateral cephalograms in subjects with skeletal Class I and skeletal Class II pattern and to investigate the gender differences. Materials and Methods: The study used lateral cephalograms of 40 subjects (20 skeletal Class I pattern; 20 skeletal Class II pattern. Lateral cephalograms were traced and analyzed for evaluation of the hyoid bone position and the head posture using 34 parameters. Independent sample t-test was performed to compare the differences between the two groups and between genders in each group. Statistical tests were performed using NCSS 2007 software (NCSST, Kaysville, Utah, USA. Results: The linear measurements between the hyoid bone (H and cervical spine (CV2ia, the nasion-sella line, palatal line nasion line, the anterior nasal spine (ANS to perpendicular projection of H on the NLP (NLP- Nasal Linear Projection (H-NLP/ANS as well as the posterior cranial points (Bo, Ar and S points were found to be less in skeletal Class II subjects. The measurement H-CV2ia was found to be less in males with skeletal Class I pattern and H-CV4ia was found to be less in males with skeletal Class II pattern. The natural head posture showed no significant gender differences. Conclusion: The position of hyoid bone was closer to the cervical vertebra horizontally in skeletal Class II subjects when compared with skeletal Class I subjects. In males, the hyoid bone position was closer to the cervical vertebra horizontally both in skeletal Class I and skeletal Class II subjects.

  9. CD8 T cell memory recall is enhanced by novel direct interactions with CD4 T cells enabled by MHC class II transferred from APCs.

    Directory of Open Access Journals (Sweden)

    Pablo A Romagnoli

    Full Text Available Protection against many intracellular pathogens is provided by CD8 T cells, which are thought to need CD4 T cell help to develop into effective memory CD8 T cells. Because murine CD8 T cells do not transcribe MHC class II (MHC-II genes, several models have proposed antigen presenting cells (APCs as intermediaries required for CD4 T cells to deliver their help to CD8 T cells. Here, we demonstrate the presence of MHC-II molecules on activated murine CD8 T cells in vitro as well as in vivo. These MHC-II molecules are acquired via trogocytosis by CD8 T cells from their activating APCs, particularly CD11c positive dendritic cells (DCs. Transferred MHC-II molecules on activated murine CD8 T cells were functionally competent in stimulating specific indicator CD4 T cells. CD8 T cells that were "helped" in vitro and subsequently allowed to rest in vivo showed enhanced recall responses upon challenge compared to "helpless" CD8 T cells; in contrast, no differences were seen upon immediate challenge. These data indicate that direct CD8:CD4 T cell interactions may significantly contribute to help for CD8 T cells. Furthermore, this mechanism may enable CD8 T cells to communicate with different subsets of interacting CD4 T cells that could modulate immune responses.

  10. Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (Ii)

    Science.gov (United States)

    2007-05-01

    uveal melanoma cells. Cancer Res. 67: 4499-4506, 2007. 30. Chamuleau ME, Souwer Y, Van Ham SM, Zevenbergen A, Westers TM, Berkhof J, Meijer CJ, van...MHC class I, class II, CD80, CD4, CD8, and immunoglobulin) or fixed and stained for Ii as described (20). Western blots . Ii Western blots were done...as described (20). Blots for MHC II were done as for Ii with the following modifications: cell lysates were loaded onto SDS-PAGE gels using nonreducing

  11. Expression of HLA Class I and HLA Class II by Tumor Cells in Chinese Classical Hodgkin Lymphoma Patients

    NARCIS (Netherlands)

    Huang, Xin; van den Berg, Anke; Gao, Zifen; Visser, Lydia; Nolte, Ilja; Vos, Hans; Hepkema, Bouke; Kooistra, Wierd; Poppema, Sibrand; Diepstra, Arjan

    2010-01-01

    Background: In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. HLA expression (in relation to EBV) in Asian cHL patients has no

  12. DIFFERENT ROLES OF CLASS-I AND CLASS-II CLOSTRIDIUM-HISTOLYTICUM COLLAGENASE IN RAT PANCREATIC-ISLET ISOLATION

    NARCIS (Netherlands)

    WOLTERS, GHJ; VOSSCHEPERKEUTER, GH; LIN, HC; VANSCHILFGAARDE, R

    1995-01-01

    Crude Clostridium histolyticum collagenase was purified by gel filtration and fractionated by anion exchange chromatography into class I with high collagen digestion activity (CDA) and low FALGPA (2-furanacryloyl-L-leucylglycyl-L-prolyI-L-alanine )hydrolysis activity (FHA), class II with low CDA and

  13. Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, C.D.; Trombone, A.P.F.; Lorenzi, J.C.C.; Almeida, L.P.; Gembre, A.F.; Padilha, E. [Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Ramos, S.G. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, C.L.; Coelho-Castelo, A.A.M. [Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-09-21

    In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.

  14. Effect of multiple genetic polymorphisms on antigen presentation and susceptibility to Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Chang, Stewart T; Linderman, Jennifer J; Kirschner, Denise E

    2008-07-01

    Several molecules related to antigen presentation, including gamma interferon (IFN-gamma) and the major histocompatibility complex (MHC), are encoded by polymorphic genes. Some polymorphisms were found to affect susceptibility to tuberculosis (TB) when they were considered singly in epidemiological studies, but how multiple polymorphisms interact to determine susceptibility to TB in an individual remains an open question. We hypothesized that polymorphisms in some genes may counteract or intensify the effects of polymorphisms in other genes. For example, an increase in IFN-gamma expression may counteract the weak binding that a particular MHC variant displays for a peptide from Mycobacterium tuberculosis to establish the same T-cell response as another, more strongly binding MHC variant. To test this hypothesis, we developed a mathematical model of antigen presentation based on experimental data for the known effects of genetic polymorphisms and simulated time courses when multiple polymorphisms were present. We found that polymorphisms in different genes could affect antigen presentation to the same extent and therefore compensate for each other. Furthermore, we defined the conditions under which such relationships could exist. For example, increased IFN-gamma expression compensated for decreased peptide-MHC affinity in the model only above a certain threshold of expression. Below this threshold, changes in IFN-gamma expression were ineffectual compared to changes in peptide-MHC affinity. The finding that polymorphisms exhibit such relationships could explain discrepancies in the epidemiological literature, where some polymorphisms have been inconsistently associated with susceptibility to TB. Furthermore, the model allows polymorphisms to be ranked by effect, providing a new tool for designing association studies.

  15. Survival and signaling changes in antigen presenting cell subsets after radiation

    Science.gov (United States)

    Parker, Jennifer Janell

    Radiation therapy is a widely used cancer treatment that has the potential to influence anti-tumor immune responses. Both myeloablative and non-myeloablative radiation are often used as part of preparatory regimens for hematopoetic stem cell transplantation, in combination with other chemotherapy or immuno-modulatory (e.g. Anti-thymocyte globulin (ATG)) therapies for both cytotoxic and immune modulatory purposes. However, the mechanisms responsible for the effect of radiation on antigen presenting cell (APC) responsiveness and radioresistance are poorly understood. The first studies described in this thesis were designed to identify and characterize early radiation-induced signaling changes in antigen presenting cells and to determine the effects of these signaling changes on APC receptor expression and function. The NFkappaB pathway in antigen presenting cells was chosen for study because it is activated by radiation in a wide range of other cell types and plays a vital role in the maintenance and regulation of the immune system. The effects of therapeutically relevant doses radiation (2 and 20 Gy) were compared at various timepoints in the human monocytic cell line (U937) using phospho-flow cytometry staining methods and cytometric analysis. These studies demonstrated that radiation-induced changes in the phosphorylation state of NFkappaB family members that were p53 independent. However, these changes were dependent upon activation of ATM in response to single or double-stranded breaks in DNA, as shown in experiments using an inhibitor of ATM and ATM siRNA knockdown U937 cells. In addition, studies examining the effect of radiation on co-stimulatory receptors with and without inhibition of the NFkappaB pathway via phospho-flow cytometry revealed that radiation-induced phosphorylation of NEMO promoted the activation and functional maturation of U937 cells. Furthermore, functional studies using both phospho-flow cytometry and/or mixed lymphocyte reactions to

  16. Management of Class I and Class II Amalgam Restorations with Localized Defects: Five-Year Results

    Directory of Open Access Journals (Sweden)

    Javier Martin

    2013-01-01

    Full Text Available Replacement of dental restorations has been the traditional treatment for defective restorations. This five-year prospective clinical trial evaluated amalgam restorations with localized defects that were treated by means of repair or refurbishing. Fifty-two patients (50% female and 50% male, mean age 28.3±18.1 years, range 18–80 with 160 class I and class II defective restorations were included. The study focused on the application of two minimally invasive treatments for localized restoration defects and compared these with no treatment and total replacement as negative and positive controls, respectively. Restorations were assessed by two calibrated examiners according to modified U.S. Public Health Service criteria, including marginal adaptation, anatomic form, secondary caries, and roughness. At five years, recall was examined in 45 patients with 108 restorations (67.5%. The results suggest that repair treatment is as effective as total replacement of restorations with localized defects, reducing biological costs to the patient and providing new tools to the clinician. Refinishing restoration is a useful treatment for localized anatomic form defects.

  17. Características cefalométricas de pacientes portadores de más oclusões Classe I e Classe II de Angle Cephalometric characteristics of patients with Angle Class I and Class II malocclusions

    Directory of Open Access Journals (Sweden)

    Rogério Lacerda dos Santos

    2009-06-01

    Full Text Available OBJETIVOS: o presente estudo comparou algumas medidas cefalométricas relacionadas às características faciais em pacientes com má oclusão Classe I, Classe II 1ª divisão e Classe II 2ª divisão. METODOLOGIA: foram selecionadas 130 telerradiografias de pacientes leucodermas em fase inicial de tratamento ortodôntico, com idades entre 10 e 16 anos (média de 12,6 anos; e divididos em 3 grupos. As medidas cefalométricas utilizadas neste estudo foram: ANB, ı-SN, IMPA, AML, Ls-ı, Li-ī e EI. A análise de variância e o teste de Tukey foram realizados nas medidas ANB, IMPA, AML, ı-SN e Li-ī. Para as demais variáveis (EI e Ls-ı foi utilizado o teste de Kruskal Wallis e Dunn. RESULTADOS: os resultados mostraram que as medidas Ls-ı e EI tiveram diferença estatisticamente significativa entre os grupos I e II-1 e entre os grupos II-1 e II-2 (p AIM: The present study compared some cephalometric measurements related to facial characteristics in patients having Class I, Class II division 1, and Class II division 2 malocclusions. METHODS: One hundred and thirty teleradiographs of Caucasian patients aged 10-16 years (mean age of 12.6 years under initial orthodontic treatment were selected for study and divided into 3 groups. The cephalometric measurements used in the present study were the following: ANB, ı-SN, IMPA, AML, Ls-ı, Li-ī, and EI. Variance analysis and Tukey's test were carried out for ANB, IMPA, AML, ı-SN, and Li-ī measurements, whereas Kruskal-Wallis and Dunn's tests were used for EI and Ls-ı. RESULTS: Statistically significant differences were found for EI and Ls-ı measurements when Group II-1 was compared to Group I and Group II-2 (p < 0.05. ANB and IMPA measurements also had statistically significant differences when Group I was compared to Group II-1 and Group II-2 (p < 0.05. The measurement ı-SN had statistically significant differences between the 3 groups (p < 0.05. CONCLUSIONS: One can conclude that the measurement

  18. II-Q restriction endonucleases--new class of type II enzymes.

    Science.gov (United States)

    Degtyarev, S K; Rechkunova, N I; Kolyhalov, A A; Dedkov, V S; Zhilkin, P A

    1990-10-11

    Unique restriction endonucleases Bpu 10l and Bsil have been isolated from Bacillus pumilas and Bacillus sphaericus, respectively. The recognition sequences and cleavage points of these enzymes have been determinated as 5'-CC1TNAGC-3'/3'-GGANT1CG-5' for Bpu 10l and 5'-C1TCGTG-3'/3'-GAGCA1C-5' for Bsil. Restriction endonucleases Bpu 10l and Bsil represent a new class of enzymes which recognize non-palindromic nucleotide sequences and hydrolize DNA within the recognition sequence. Bpu 10l and Bsil recognition sequences may be regarded as quasipalindromic and the enzymes may be designated as type II-Q restriction endonucleases.

  19. Allogeneic T cells induce rapid CD34+ cell differentiation into CD11c+CD86+ cells with direct and indirect antigen-presenting function

    Science.gov (United States)

    Abbasian, Javaneh; Mahmud, Dolores; Mahmud, Nadim; Chunduri, Sandeep; Araki, Hiroto; Reddy, Pavan; Hoffman, Ronald; Arpinati, Mario; Ferrara, James L. M.; Rondelli, Damiano

    2006-01-01

    Dendritic cells (DCs) derive from CD34+ cells or monocytes and stimulate alloimmune responses in transplantation. We hypothesized that the interaction between CD34+ cells and allogeneic T cells would influence the function of hematopoietic stem cells (HSCs). Cord blood (CB) CD34+ cells proliferated briskly in response to allogeneic, but not autologous, T cells when mixed with irradiated T cells for 6 days in vitro. This proliferation was significantly inhibited by an anti-HLA class II monoclonal antibody (mAb), by an anti-TNFα mAb, or by CTLA4-Ig. Allogeneic T cells induced the differentiation of CD34+ progenitors into cells with the morphology of dendritic monocytic precursors and characterized by the expression of HLA-DR, CD86, CD40, CD14, and CD11c, due to an endogenous release of TNFα. Cotransplantation of CD34+ cells with allogeneic T cells into nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice resulted in a greater engraftment of myeloid CD1c+ dendritic cells compared with cotransplantation with autologous T cells. In vitro, CD34+ cell-derived antigen-presenting cells (APCs) were functionally capable of both direct and indirect presentation of alloantigens. Based on these findings, we hypothesize that in HSC transplantation the initial cross talk between allogeneic T cells and CD34+ cells may result in the increased generation of APCs that can present host alloantigens and possibly contribute to the development of graft-versus-host disease. (Blood. 2006;108:203-208) PMID:16478883

  20. Performance assessment for the class L-II disposal facility

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This draft radiological performance assessment (PA) for the proposed Class L-II Disposal Facility (CIIDF) on the Oak Ridge Reservation (ORR) has been prepared to demonstrate compliance with the requirements of the US Department of Energy Order 5820.2A. This PA considers the disposal of low-level radioactive wastes (LLW) over the operating life of the facility and the long-term performance of the facility in providing protection to public health and the environment. The performance objectives contained in the order require that the facility be managed to accomplish the following: (1) Protect public health and safety in accordance with standards specified in environmental health orders and other DOE orders. (2) Ensure that external exposure to the waste and concentrations of radioactive material that may be released into surface water, groundwater, soil, plants, and animals results in an effective dose equivalent (EDE) that does not exceed 25 mrem/year to a member of the public. Releases to the atmosphere shall meet the requirements of 40 CFR Pt. 61. Reasonable effort should be made to maintain releases of radioactivity in effluents to the general environment as low as reasonably achievable. (1) Ensure that the committed EDEs received by individual who inadvertently may intrude into the facility after the loss of active institutional control (100 years) will not exceed 100 mrem/year for continuous exposure of 500 mrem for a single acute exposure. (4) Protect groundwater resources, consistent with federal, state, and local requirements.

  1. MHC class II polymorphisms, autoreactive T-cells and autoimmunity

    Directory of Open Access Journals (Sweden)

    Sue eTsai

    2013-10-01

    Full Text Available Major histocompatibility complex (MHC genes, also known as human leukocyte antigen genes (HLA in humans, are the prevailing contributors of genetic susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D, Multiple Sclerosis (MS, and Rheumatoid arthritis (RA, among others (Todd and Wicker, 2001;MacKay et al., 2002;Hafler et al., 2007. Although the pathways through which MHC molecules afford autoimmune risk or resistance remain to be fully mapped out, it is generally accepted that they do so by shaping the central and peripheral T cell repertoires of the host towards autoimmune proclivity or resistance, respectively. Disease-predisposing MHC alleles would both spare autoreactive thymocytes from central tolerance and bias their development towards a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote central deletion of autoreactive thymocytes and skew their development towards non-pathogenic phenotypes. This interpretation of the data is at odds with two other observations: that in MHC-heterozygous individuals, resistance is dominant over susceptibility; and that it is difficult to understand how deletion of one or a few clonal autoreactive T cell types would suffice to curb autoimmune responses driven by hundreds if not thousands of autoreactive T cell specificities. This review provides an update on current advances in our understanding of the mechanisms underlying MHC class II-associated autoimmune disease susceptibility and/or resistance and attempts to reconcile these seemingly opposing concepts.

  2. Antigen presenting cells costimulatory signaling during pre-implantation pregnancy 

    Directory of Open Access Journals (Sweden)

    Anna Sławek

    2012-09-01

    Full Text Available  Success of pregnancy depends on many factors. Three phenomena inducing immune tolerance against semi-allogeneic conceptus may play a crucial role in the pre-implantation period of pregnancy: influence of sex hormones in sex cycle, presence of oocyte or embryo and the presence of semen in the female reproductive tract. On the other hand dendritic cells are the most effective antigen-presenting cells in regulation of immune phenomena and also are considered as potent participants in inducing immune tolerance in the pregnancy. They communicate with T cells in cell contact-dependent manner or via cytokines. During cell-cell contacts, costimulatory molecules play a key role and their expression is often dependent on cytokines milieu. Both costimulatory molecules and cytokines influence generation of T regulatory cells. Interactions of these molecules are closely related. In this paper we would like to pay attention to the importance of antigen presenting cells costimulatory potency in immune regulation during a pre-implantation period of pregnancy.

  3. Exosomes function in antigen presentation during an in vivo Mycobacterium tuberculosis infection

    Science.gov (United States)

    Smith, Victoria L.; Cheng, Yong; Bryant, Barry R.; Schorey, Jeffrey S.

    2017-01-01

    Mycobacterium tuberculosis-infected macrophages and dendritic cells are limited in their ability to present antigen to CD4+ T cells suggesting that other mechanism of antigen presentation are driving the robust T cell response observed during an M. tuberculosis infection. These mechanisms could include antigens present in apoptotic bodies, necrotic debris, exosomes or even release of non-vesicular antigen from infected cells. However, there is limited data to support any of these mechanisms as important in driving T cell activation in vivo. In the present study we use Rab27a-deficient mice which show diminished trafficking of mycobacterial components to exosomes as well as M. tuberculosis strains that express recombinant proteins which traffic or fail to traffic to exosomes. We observed that exosomes released during a mouse M. tuberculosis infection contribute significantly to its T cell response. These finding imply that exosomes function to promote T cell immunity during a bacterial infection and are an important source of extracellular antigen. PMID:28262829

  4. Effects of antigen presentation of eosinophils on lung Th1/Th2 imbalance

    Institute of Scientific and Technical Information of China (English)

    XIE Zheng-fu; SHI Huan-zhong; QIN Xue-jun; KANG Lan-fu; HUANG Chun-ping; CHEN Yi-qiang

    2005-01-01

    Background Antigen-loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2-type cytokine production in the draining lymph nodes. The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues.Methods Airway EOSs were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these EOSs were then cocultured with CD4+ cells isolated from sensitized mice in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines.Results Airway EOSs functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate lung CD4+ lymphocytes to produce interleukin-4, interleukin-5 and interleukin-13, but not interferon-γ in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin-4, interleukin-5 and interleukin-13, but not interferon-γ, production during the in vitro culture that was also CD80- and CD86-dependent. Conclusion EOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells in the lungs.

  5. Antigen presenting cells in the skin of a patient with hair loss and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2009-01-01

    Full Text Available Context: Hair loss is one of the most striking clinical features of active systemic lupus erythematosus (SLE, however, very few studies have investigated the immunological features of this process. Case report: We describe a 33 years old female who presented with scalp hair loss and arthralgias. Physical examination revealed erythematous plaques on the nose and scalp, with bitemporal hair loss. Scalp biopsies revealed epidermal hyperkeratosis, with a mild interface infiltrate of lymphocytes and histiocytes and a superficial and deep, perivascular and periadnexal infiltrate of mostly CD4 positive cells. Antibodies to HAM 56, CD68, CD1a, S-100, mast cell tryptase and c-kit/CD117 were strongly positive around the hair follicles, and in the adjacent sebaceous glands. Conclusion : We present the first report showing a significant presence of several antigen presenting cells around the hair follicular units in a patient with alopecia in active SLE. Today, antigen presenting cells and dendritic cells (DC are modeled as the master regulators of human immunity. One aspect that has become clearly appreciated is the great diversity of DC subtypes, each with considerable functional differences. Thus, we suggest that APC and DCs are equipped with Pattern Recognition Receptors (PRRs to some hair follicular unit antigens; that these innate sensors recognize conserved molecular patterns on self- tissue, and play a significant role in the pathophysiology of alopecia in SLE patients

  6. 77 FR 60625 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2012-10-04

    ... National Indian Gaming Commission 25 CFR Parts 542 and 543 RIN 3141-AA-37 Minimum Internal Control... while tribes and operations transition to the new Class II Minimum Internal Control Standards that were... part 543, Minimum Internal Control Standards Class II Gaming, with comprehensive and updated...

  7. 76 FR 53817 - Minimum Internal Control Standards for Class II Gaming

    Science.gov (United States)

    2011-08-30

    ... National Indian Gaming Commission 25 CFR Parts 542 and 543 Minimum Internal Control Standards for Class II... delay of the effective date on the final rule for Minimum Internal Control Standards for Class II Gaming... sections of established Minimum Internal Control Standards and replaced them with a new part titled...

  8. Long-term evaluation of Class II subdivision treatment with unilateral maxillary first molar extraction

    NARCIS (Netherlands)

    Livas, Christos; Pandis, Nikolaos; Booij, Johan Willem; Katsaros, Christos; Ren, Yijin

    2015-01-01

    Objective: To evaluate the long-term effects of asymmetrical maxillary first molar (M1) extraction in Class II subdivision treatment. Materials and Methods: Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0 years; SD, 1.7 years) consecutively treated with the Begg technique

  9. Maxillary first molar extraction in Class II malocclusion : Follow-up studies on treatment effects

    NARCIS (Netherlands)

    Livas, Christos

    2015-01-01

    This PhD research investigated treatment effects of extraction of one and two maxillary first molars in Class II subdivision and Class II/1 malocclusion cases respectively from a longer time perspective. Private practice records were scrutinized to evaluate aspects of a treatment technique combining

  10. 40 CFR 144.22 - Existing Class II enhanced recovery and hydrocarbon storage wells.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells. 144.22 Section 144.22 Protection of Environment ENVIRONMENTAL... of Underground Injection by Rule § 144.22 Existing Class II enhanced recovery and hydrocarbon storage wells. (a) An existing Class II enhanced recovery or hydrocarbon storage injection well is authorized...

  11. The effectiveness of different polymerization protocols for class II composite resin restorations.

    NARCIS (Netherlands)

    Jong, L.C.G. de; Opdam, N.J.M.; Bronkhorst, E.M.; Roeters, F.J.M.; Wolke, J.G.C.; Geitenbeek, B.

    2007-01-01

    OBJECTIVES: To investigate the effect of reduced light exposure times on Vickers hardness (VH) of class II composite resin restorations. METHODS: Class II restorations were made in vitro in three 2mm thick increments in a human molar. Two composite resins (Clearfil AP-X; Esthet-X) were polymerized w

  12. Insect Cells Encode a Class II α-Mannosidase with Unique Properties*

    OpenAIRE

    Kawar, Ziad; Karaveg, Khanita; Moremen, Kelley W.; Jarvis, Donald L.

    2001-01-01

    Previously, we cloned and characterized an insect (Sf9) cell cDNA encoding a class II α-mannosidase with amino acid sequence and biochemical similarities to mammalian Golgi α-mannosidase II. Since then, it has been demonstrated that other mammalian class II α-mannosidases can participate in N-glycan processing. Thus, the present study was performed to evaluate the catalytic properties of the Sf9 class II α-mannosidase and to more clearly determine its relationship to mammalian Golgi α-mannosi...

  13. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells

    Institute of Scientific and Technical Information of China (English)

    Ho-Keun Kwon; Zee Yong Park; Sin-Hyeog Im; Ji-Sun Hwang; Choong-Gu Lee; Jae-Seon So; Anupama Sahoo; Chang-Rok Im; Won Kyung Jeon; Byoung Seob Ko; Sung Haeng Lee

    2011-01-01

    AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells. METHODS:Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7),mouse primary antigen-presenting cells (APCs,MHCII+) and CD11c+ dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo ,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression profiles in inflamed tissue. RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase (COX)-2.Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β,IL-6,IL-12,interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β).In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro

  14. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Coeliac disease (CD is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1, DQ6(1, DR11(5, DQ7(3, DQ2 and DR15(2 were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2 was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1 and DQ6(1 in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5 in the group of relatives (RR=0.363,PF=0.232. These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.

  15. Phenotypic Diversity in Caucasian Adults with Moderate to Severe Class II Malocclusion

    Science.gov (United States)

    Moreno Uribe, Lina M.; Howe, Sara C.; Kummet, Colleen; Vela, Kaci C.; Dawson, Deborah V.; Southard, Thomas E.

    2014-01-01

    INTRODUCTION Class II malocclusion affects about 15 % of the US population and is characterized by a convex profile and occlusion disharmonies. The specific etiological mechanisms resulting in the range of Class II dento-skeletal combinations observed is not yet understood. Most studies describing the class II phenotypic diversity have utilized moderate sample sizes or have focused on younger individuals that later in life may outgrow their class II discrepancies; such a focus may also preclude the visualization of adult class II features. The majority have utilized simple correlation methods resulting in phenotypes that may not be generalizable to different samples and thus may not be suitable for studies of malocclusion etiology. The purpose of this study is to address these knowledge gaps by capturing the maximum phenotypic variation present in a large Caucasian sample of class II individuals selected with strict eligibility criteria and rigorously standardized multivariate reduction analyses. METHODS Sixty-three lateral cephalometric variables were measured from pre-treatment records of 309 Class II Caucasian adults (82 males, 227 females; ages 16–60 years). Principal component analysis (PCA) and cluster analysis were used to generate comprehensive phenotypes in an effort to identify the most homogeneous groups of individuals reducing heterogeneity and improving the power of future malocclusion etiology studies. RESULTS PCA resulted in 7 principal components that accounted for 81% of the variation. The first three components represented variation on mandibular rotation, upper incisor angulation and mandibular length, respectively. The cluster analysis identified 5 distinct Class II phenotypes. CONCLUSIONS A comprehensive spectrum of Class II phenotypic definitions was obtained that could be generalized to other samples advancing our efforts to the identification of etiological factors underlying Class II malocclusion. PMID:24582022

  16. Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

    Science.gov (United States)

    Shenoda, Botros B.; Ajit, Seena K.

    2016-01-01

    Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages. PMID:27660518

  17. Immunology by numbers: quantitation of antigen presentation completes the quantitative milieu of systems immunology!

    Science.gov (United States)

    Purcell, Anthony W; Croft, Nathan P; Tscharke, David C

    2016-06-01

    We review approaches to quantitate antigen presentation using a variety of biological and biochemical readouts and highlight the emerging role of mass spectrometry (MS) in defining and quantifying MHC-bound peptides presented at the cell surface. The combination of high mass accuracy in the determination of the molecular weight of the intact peptide of interest and its signature pattern of fragmentation during tandem MS provide an unambiguous and definitive identification. This is in contrast to the potential receptor cross-reactivity towards closely related peptides and variable dose responsiveness seen in biological readouts. In addition, we gaze into the not too distant future where big data approaches in MS can be accommodated to quantify whole immunopeptidomes both in vitro and in vivo.

  18. CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Ellen J Beswick; Victor E Reyes

    2009-01-01

    CD74 is a protein whose initial role in antigen presentation was recognized two decades ago. Recent studies have revealed that it has additional functions as a receptor for macrophage migration inhibitory factor and as a receptor for an important human pathogen, Helicobacter pylori ( H pylori). The role of CD74 as a receptor is important because after binding of migration inhibitory factor or H pylori, NF-kB and Erk1/2 activation occurs, along with the induction of proinflammatory cytokine secretion. This review provides an up-to-date account of the functions of CD74 and how it might be involved in inflammation and cancer within the gastrointestinal tract.

  19. HAM56 and CD68 antigen presenting cells surrounding a sarcoidal granulomatous tattoo

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2011-01-01

    Full Text Available Context : Tattoos are produced by introducing colorants of various compositions into the skin, either accidentally or for cosmetic purposes. Case Report: A 62-year-old male presented with a cosmetic tattoo and requested a total excision of the lesion. Dermatopathologic analysis of the excised tissue with hematoxylin and eosin examination, as well as immunohistochemistry was performed. H&E staining demonstrated classic histologic features of a tattoo. Utilizing immunohistochemistry, dermal histiocytic antigen presenting cells stained with HAM56 and CD68 antibodies; the staining was present surrounding the tattoo pigment. Conclusions : We identified two macrophage markers (HAM56 and CD68 surrounding dermal tattoo pigment. A minimal dermal inflammatory immune was noted to the tattoo pigment. Moreover, the immune response and/or tolerance to tattoos is not well characterized. We suggest that tattoo materials and techniques could be utilized in therapeutic delivery for diseases such recessive dystrophic epidermolysis bullosa, potentially preventing immune rejection of gene therapy agents.

  20. An Overview of B-1 Cells as Antigen-Presenting Cells

    Science.gov (United States)

    Popi, Ana F.; Longo-Maugéri, Ieda M.; Mariano, Mario

    2016-01-01

    The role of B cells as antigen-presenting cells (APCs) has been extensively studied, mainly in relation to the activation of memory T cells. Considering the B cell subtypes, the role of B-1 cells as APCs is beginning to be explored. Initially, it was described that B-1 cells are activated preferentially by T-independent antigens. However, some reports demonstrated that these cells are also involved in a T-dependent response. The aim of this review is to summarize information about the ability of B-1 cells to play a role as APCs and to briefly discuss the role of the BCR and toll-like receptor signals in this process. Furthermore, some characteristics of B-1 cells, such as natural IgM production and phagocytic ability, could interfere in the participation of these cells in the onset of an adaptive response. PMID:27148259

  1. Criculating fibrocytes: a potent cell population in antigen-presenting and wound healing

    Institute of Scientific and Technical Information of China (English)

    FAN Xia; LIANG Hua-ping

    2010-01-01

    Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers ofmonocytic lineage as well as fibro-blast products.During wound healing, fibrocytes have been found to possess the ability of antigen-presentation to naive T cells in the inflammatory phase.Moreover, they can pro-mote the endothelial cell proliferation, migration and angio-genesis by secreting several proteins.Fibrocytes can fur-ther differentiate into mature mesenchymocyte lineage, suchas fibroblasts, myofibroblasts and adipocytes, and they may represent the systemic source of myofibroblasts that exert a contractile force required to close tissue wounds.A deep understanding of the mechanism involved in fibrocyte mi-gration and differentiation may lead to the development of a novel theory of normal physiology and pathology.

  2. Induction of anti-tumor CD8 T cell responses by experimental ECP-induced human dendritic antigen presenting cells.

    Science.gov (United States)

    Kibbi, N; Sobolev, O; Girardi, M; Edelson, R L

    2016-08-01

    Extracorporeal photochemotherapy (ECP), or photopheresis, is distinguished by the specificity of the clinically potent immunologic reactions it initiates or regulates. The selectivity of ECP-induced immunoprotection for the malignant clone in cutaneous T cell lymphoma (CTCL), and for the pathogenic clones in allograft rejection and graft-versus-host disease (GVHD), has suggested a central mechanistic role for dendritic antigen presenting cells (DC). Discovery of ECP's induction of monocyte-derived DC, via monocyte signaling by ECP-plate activated platelets, and the absolute dependency of experimental ECP on such induced DC, supports that premise. Herein, we show that ECP-induced DC are capable of stimulating CD8 T cell responses to tumor antigens with which they are loaded. They internalize an antigen-specific melanoma-associated protein then present it onto a class I major histocompatibility, which then stimulates expansion of anti-tumor CD8 T cell populations. We conclude that ECP-induced DC prominently contribute to its initiation of anti-tumor immunity and raise the possibility that the therapy may be applicable to the immunotherapeutic management of a broader spectrum of cancers.

  3. Class II antigen-associated invariant chain mRNA in mouse small intestine.

    Science.gov (United States)

    Ouellette, A J; Frederick, D; Hagen, S J; Katz, J D

    1991-09-30

    MHC class II antigen-associated invariant (Ii) chain mRNA appears in mouse small intestine during postnatal development. Ii chain cDNA hybridizes to RNA from epithelial sheets dissociated from the lamina propria with EDTA. Of several mouse organs tested, only bone marrow and spleen contain higher levels of Ii chain mRNA than small bowel. Ii chain mRNA is not detected in stomach, colon, duodenum, testis, liver, submandibular gland, or L-cell RNA; brain contains a cross-reactive but uncharacterized sequence. cDNA amplification using primers specific for both Ii31 and Ii41 chain mRNAs showed that both forms occur in small intestine. These results support the conclusion that regulation of the class II Ii chain gene is associated with the ontogeny of intestinal immunity.

  4. Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma.

    Science.gov (United States)

    Klein-González, Nela; Holtick, Udo; Fairfax, Kirsten; Weihrauch, Martin R; von Bergwelt-Baildon, Michael S

    2011-03-01

    Evaluation of: Brody JD, Ai WZ, Czerwinski DK et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324-4332 (2010). Despite high response rates of the follicular B-cell lymphoma to monoclonal antibodies, the clinical course of lymphoma is still characterized by a continuous pattern of relapse. Brody and colleagues treated 15 patients with relapsed, low-grade lymphoma using low-dose radiotherapy applied to one of the tumor sites with combined injection of a TLR-9 agonist at the same site. This strategy induced specific immunity and tumor regression in several patients with an objective response rate of 27%. The results indicate an involvement of the tumor TLR-9-expressing B cells acting as antigen-presenting cells. TLR-9 in situ vaccination combined with local radiotherapy clearly warrants further in-depth analysis and investigation in a Phase III randomized trial, and may provide a new opportunity for the treatment of B-cell malignancies.

  5. HLA-DR+ Immature Cells Exhibit Reduced Antigen-Presenting Cell Function But Respond to CD40 Stimulation

    Directory of Open Access Journals (Sweden)

    Alberto Pinzon-Charry

    2005-12-01

    Full Text Available Dendritic cells (DC have been implicated in the defective function of the immune system during cancer progression. We have demonstrated that patients with cancer have fewer myeloid (CD11c+ and plasmacytoid (CD123hi DC and a concurrent accumulation of CD11c−CD123− immature cells expressing HLA-DR (DR+IC. Notably, DR+IC from cancer patients have a reduced capacity to stimulate allogeneic T-cells. DR+IC are also present in healthy donors, albeit in smaller numbers. In this study, we assessed whether DR+IC could have an impact on the immune response by comparing their function with DC counterparts. For this purpose, DR+IC and DC were purified and tested in the presentation of antigens through major histocompatibility complex (MHC II and MHC-I molecules. DR+IC were less efficient than DC at presenting antigens to T-cells. DR`IC induced a limited activation of T-cells, eliciting poor T-helper (Th 1 and preferentially inducing Th2-biased responses. Importantly, despite DR+IC's poor responsiveness to inflammatory factors, in samples from healthy volunteers and breast cancer patients, CD40 ligation induced phenotypic maturation and interleukin 12 secretion, in turn generating more efficient T-cell responses. These data underscore the importance of inefficient antigen presentation as a mechanism for tumor evasion and suggest an approach to improve the efficacy of DC-based immunotherapy for cancer.

  6. CITA/NLRC5: A critical transcriptional regulator of MHC class I gene expression.

    Science.gov (United States)

    Downs, Isaac; Vijayan, Saptha; Sidiq, Tabasum; Kobayashi, Koichi S

    2016-07-08

    Major histocompatibility complex (MHC) class I and class II molecules play essential roles in the development and activation of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator) has been recognized as a master regulator of MHC class II gene expression, albeit knowledge about the regulatory mechanism of MHC class I gene expression had been limited. Recently identified MHC class I transactivator (CITA), or NLRC5, also belongs to the NLR protein family and constitutes a critical regulator for the transcriptional activation of MHC class I genes. In addition to MHC class I genes, CITA/NLRC5 induces the expression of β2 -microglobulin, TAP1 and LMP2, essential components of the MHC class I antigen presentation pathway. Therefore, CITA/NLRC5 and CIITA are transcriptional regulators that orchestrate the concerted expression of critical components in the MHC class I and class II pathways, respectively. © 2016 BioFactors, 42(4):349-357, 2016.

  7. The Oropharyngeal Airway in Young Adults with Skeletal Class II and Class III Deformities: A 3-D Morphometric Analysis.

    Directory of Open Access Journals (Sweden)

    Yasas Shri Nalaka Jayaratne

    Full Text Available 1 To determine the accuracy and reliability of an automated anthropometric measurement software for the oropharyngeal airway and 2 To compare the anthropometric dimensions of the oropharyngeal airway in skeletal class II and III deformity patients.Cone-beam CT (CBCT scans of 62 patients with skeletal class II or III deformities were used for this study. Volumetric, linear and surface area measurements retroglossal (RG and retropalatal (RP compartments of the oropharyngeal airway was measured with the 3dMDVultus software. Accuracy of automated anthropometric pharyngeal airway measurements was assessed using an airway phantom.The software was found to be reasonably accurate for measuring dimensions of air passages. The total oropharyngeal volume was significantly greater in the skeletal class III deformity group (16.7 ± 9.04 mm3 compared with class II subjects (11.87 ± 4.01 mm3. The average surface area of both the RG and RP compartments were significantly larger in the class III deformity group. The most constricted area in the RG and RP airway was significantly larger in individuals with skeletal class III deformity. The anterior-posterior (AP length of this constriction was significantly greater in skeletal class III individuals in both compartments, whereas the width of the constriction was not significantly different between the two groups in both compartments. The RP compartment was larger but less uniform than the RG compartment in both skeletal deformities.Significant differences were observed in morphological characteristics of the oropharyngeal airway in individuals with skeletal class II and III deformities. This information may be valuable for surgeons in orthognathic treatment planning, especially for mandibular setback surgery that might compromise the oropharyngeal patency.

  8. B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis.

    Science.gov (United States)

    Parker Harp, Chelsea R; Archambault, Angela S; Sim, Julia; Ferris, Stephen T; Mikesell, Robert J; Koni, Pandelakis A; Shimoda, Michiko; Linington, Christopher; Russell, John H; Wu, Gregory F

    2015-06-01

    B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis, in part as a result of the success of B cell-depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. Although B cell Ag presentation was suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support Ag-specific autoimmune responses by CD4 T cells in EAE is lacking. Using a newly developed murine model of in vivo conditional expression of MHC class II, we reported previously that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the sole APC. In this study, we find that B cells cooperate with dendritic cells to enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive EAE in mice expressing MHCII by B cells alone. These data support a model in which expansion of Ag-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and have the capacity to independently drive neuroinflammation at later stages of disease.

  9. Inflammatory bowel disease associations with HLA Class II genes

    Energy Technology Data Exchange (ETDEWEB)

    Castro, R. [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Yang, H.; Targan, S. [Roche Molecular Systems, Inc., Alameda, CA (United States)] [and others

    1994-09-01

    A PCR-SSOP assay has been used to analyze HLA-Class II DRB1 and DQB1 alleles in 378 Caucasians from a population in Southern California. The data has been analyzed separately for the Ashkenasi Jews and non-Jewish patients (n=286) and controls (n=92). Two common clinical forms of inflammatory bowel disease (IBD) have been studied: ulcerative colitis (UC) and Crohn`s disease (CD). In CD, we observed a susceptible effect with the rare DR1 allele - DRB*0103 [O.R.=4.56; 95% CI (0.96, 42.97); p=0.03]; a trend for an increase in DRB1*0103 was also observed in UC patients. A susceptible effect with DRB1*1502 [O.R.=5.20; 95% CI (1.10, 48.99); p=0.02] was observed in non-Jewish UC patients. This susceptible effect was restricted to UC ANCA-positive (antineutrophil cytoplasmic antibodies) patients. In addition, a significant association with DRB1*1101-DQB1*0301 [O.R.=9.46; 95% CI (1.30, 413.87); p=0.01] was seen with UC among non-Jewish patients: this haplotype was increased with CD among non-Jewish patients. Two protective haplotypes were detected among CD non-Jewish patients: DRB1*1301-DQB1*0603 [O.R.=0.34; 95% CI (0.09, 1.09); p=0.04], and DRB*0404-DQB1*0302 [O.R.=<0.08; 95% CI (0.0, 0.84); p=0.01]. When the same data were analyzed at the serology level, we observed a positive association in UC with DR2 [O.R.6.77; 95% CI (2.47, 22.95); p=2 x 10{sup -4}], and a positive association in CD with DR1 [O.R.=2.63; 95% CI (1.14, 6.62); p=0.01] consistent with previous reports. Thus, some IBD disease associations appear to be common to both UC and CD, while some are unique to one disease.

  10. Downregulation of class II transactivator (CIITA) expression by synthetic cannabinoid CP55,940.

    Science.gov (United States)

    Gongora, Celine; Hose, Stacey; O'Brien, Terrence P; Sinha, Debasish

    2004-01-30

    Cannabinoid receptors are known to be expressed in microglia; however, their involvement in specific aspects of microglial immune function has not been demonstrated. Many effects of cannabinoids are mediated by two G-protein coupled receptors, designated CB1 and CB2. We have shown that the CB1 receptor is expressed in microglia that also express MHC class II antigen (J. Neuroimmunol. 82 (1998) 13-21). In our present study, we have analyzed the effect of cannabinoid agonist CP55,940 on MHC class II expression on the surface of IFN-gamma induced microglial cells by flow cytometry. CP55,940 blocked the class II MHC expression induced by IFN-gamma. It has been shown that the regulation of class II MHC genes occurs primarily at the transcriptional level, and a non-DNA binding protein, class II transactivator (CIITA), has been shown to be the master activator for class II transcription. We find that mRNA levels of CIITA are increased in IFN-gamma induced EOC 20 microglial cells and that this increase is almost entirely eliminated by the cannabinoid agonist CP55,940. These data suggests that cannabinoids affect MHC class II expression through actions on CIITA at the transcriptional level.

  11. On the Relationship of UC H II Regions and Class II Methanol Masers: I. Source Catalogs

    CERN Document Server

    Hu, Bo; Wu, Yuanwei; Bartkiewicz, Anna; Rygl, Kazi; Reid, Mark J; Urquhart, James S; Zheng, Xingwu

    2016-01-01

    We conducted VLA C-configuration observations to measure positions and luminosities of Galactic Class II 6.7 GHz methanol masers and their associated ultra-compact H II regions. The spectral resolution was 3.90625 kHz and the continuum sensitivity reached 45 \\uJypb. We mapped 372 methanol masers with peak flux densities of more than 2 Jy selected from the literature, 367 of them were detected. Absolute positions have nominal uncertainties of 0.3 arcsec. In this first paper on the data analysis, we present three catalogs, the first gives information on the strongest feature of 367 methanol maser sources, and the second on all detected maser spots. The third catalog present derived data of the 279 radio continuum sources found in the vicinity of maser sources. Among them, 140 show evidence of physical association with maser sources. Our catalogs list properties including distance, flux density, radial velocity and the distribution of masers on the Galactic plane is then provided as well. We found no significant...

  12. Exposing the specific roles of the invariant chain isoforms in shaping the MHC class II peptidome

    OpenAIRE

    Jean-Simon eFortin; Maryse eCloutier; Jacques eThibodeau

    2013-01-01

    The peptide repertoire (peptidome) associated with MHC class II molecules (MHCIIs) is influenced by the polymorphic nature of the peptide binding groove but also by cell-intrinsic factors. The invariant chain (Ii) chaperones MHCIIs, affecting their folding and trafficking. Recent discoveries relating to Ii functions have provided insights as to how it edits the MHCII peptidome. In humans, the Ii gene encodes four different isoforms for which structure-function analyses have highlighted common...

  13. Use of cyanoacrylate as barrier in guided tissue regeneration in class II furcation defects

    Directory of Open Access Journals (Sweden)

    Carmen L Mueller Storrer

    2014-01-01

    Full Text Available The guided bone regeneration (GBR is a technique that uses resorbable and non-resorbable membranes in association with other filling biomaterials. GBR is one of the optional treatments for therapy of class II furcation defects. The current case report evaluates clinically and radiographically the use of the cyanoacrylate membrane (Glubran ®2 associated with organic bovine bone (GenOx for the treatment of vestibular class II furcation defect on the lower left molar. Conclusion: The GBR is an option in the treatment of vestibular class II furcation defects and cyanoacrylate surgical glue, acting as a mechanic barrier and providing an efficient stability for the graft.

  14. A randomized controlled 27 years follow up of three resin composites in Class II restorations

    DEFF Research Database (Denmark)

    Pallesen, Ulla; van Dijken, Jan WV

    2015-01-01

    Objective: To evaluate the durability of three conventional resin composites in Class II restorations during 27 years. Methods: Thirty participants, 25 female and 5 male (mean age 38.2 years, range 25–63), received at least three (one set) as similar as possible Class II restorations of moderate...... sealing of the restorations was performed after finishing. One operator placed 99 restorations (33 sets). Evaluation was performed with slightly modified USPHS criteria at baseline, 2, 3, 10 and 27 years. Results: Postoperative sensitivity was observed in 5 patients. Three participants with 11......: Class II restorations of the three conventional resin composites showed an acceptable success rate during the 27 year evaluation....

  15. Class II direct composite resin restorations with beta-quartz glass-ceramic inserts.

    Science.gov (United States)

    Rada, R E

    1993-11-01

    With the increasing demand for esthetic posterior restorations, numerous techniques have been developed. The direct resin restoration has probably been used most extensively in Class II situations. Problems with Class II direct resin restorations include difficulty in developing proximal contact, occlusal wear, and polymerization shrinkage. Beta-quartz glass-ceramic inserts have been developed in an attempt to reduce the incidence of these potential problems. They can be placed in a one-appointment technique, are relatively inexpensive, and can readily be utilized by the clinician adept in placing Class II composite resin restorations.

  16. Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases.

    Science.gov (United States)

    Arase, Hisashi

    2016-01-01

    Misfolded proteins localized in the endoplasmic reticulum are degraded promptly and thus are not transported outside cells. However, misfolded proteins in the endoplasmic reticulum are rescued from protein degradation upon association with major histocompatibility complex (MHC) class II molecules and are transported to the cell surface by MHC class II molecules without being processed to peptides. Studies on the misfolded proteins rescued by MHC class II molecules have revealed that misfolded proteins associated with MHC class II molecules are specific targets for autoantibodies produced in autoimmune diseases. Furthermore, a strong correlation has been observed between autoantibody binding to misfolded proteins associated with MHC class II molecules and the autoimmune disease susceptibility conferred by each MHC class II allele. These new insights into MHC class II molecules suggest that misfolded proteins rescued from protein degradation by MHC class II molecules are recognized as "neo-self" antigens by immune system and are involved in autoimmune diseases as autoantibody targets.

  17. MHC class II tetramers made from isolated recombinant α and β chains refolded with affinity-tagged peptides

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Justesen, Sune Frederik Lamdahl; Osterbye, Thomas;

    2013-01-01

    Targeting CD4+ T cells through their unique antigen-specific, MHC class II-restricted T cell receptor makes MHC class II tetramers an attractive strategy to identify, validate and manipulate these cells at the single cell level. Currently, generating class II tetramers is a specialized undertaking...... effectively limiting their use and emphasizing the need for improved methods of production. Using class II chains expressed individually in E. coli as versatile recombinant reagents, we have previously generated peptide-MHC class II monomers, but failed to generate functional class II tetramers. Adding...... a monomer purification principle based upon affinity-tagged peptides, we here provide a robust method to produce class II tetramers and demonstrate staining of antigen-specific CD4+ T cells. We also provide evidence that both MHC class II and T cell receptor molecules largely accept affinity-tagged peptides...

  18. Histochemical analysis of the role of class I and class II Clostridium histolyticum collagenase in the degradation of rat pancreatic extracellular matrix for islet isolation

    NARCIS (Netherlands)

    VosScheperkeuter, GH; vanSuylichem, PTR; Wolters, GHJ; vanSchilfgaarde, R

    1997-01-01

    To understand why class II Clostridium histolyticum collagenase is much more effective than class I in the isolation of rat pancreatic islets, we analyzed the role of these collagenases in pancreatic tissue dissociation. Crude collagenase was purified and then fractionated into class I and II with d

  19. A Case of Probable MHC Class II Deficiency with Disseminated BCGitis.

    Science.gov (United States)

    Alyasin, Soheyla; Abolnezhadian, Farhad; Khoshkhui, Maryam

    2015-09-01

    Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency disease characterized by abnormality of MHC class II molecules surface expression on peripheral blood lymphocytes and monocytes. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections but the immunodeficiency is not as severe as SCID (severe combined immunodeficiency), as evidenced by failure to develop disseminated infection after BCG vaccination. Therefore, MHC II deficiency with BCGosis, that is disseminated BCGitis, is not reported commonly. We report an interesting case of BCGosis after vaccination that was diagnosed to have probable MHC II deficiency.

  20. Cowpox virus employs a two-pronged strategy to outflank MHCI antigen presentation.

    Science.gov (United States)

    McCoy, William H; Wang, Xiaoli; Yokoyama, Wayne M; Hansen, Ted H; Fremont, Daved H

    2013-09-01

    Smallpox decimated humanity for thousands of years before being eradicated by vaccination, a success facilitated by the fact that humans are the only host of variola virus. In contrast, other orthopoxviruses such as cowpox virus can infect a variety of mammalian species, although its dominant reservoir appears to be rodents. This difference in host specificity suggests that cowpox may have developed promiscuous immune evasion strategies to facilitate zoonosis. Recent experiments have established that cowpox can disrupt MHCI antigen presentation during viral infection of both human and murine cells, a process enabled by two unique proteins, CPXV012 and CPXV203. While CPXV012 inhibits antigenic peptide transport from the cytosol to the ER, CPXV203 blocks MHCI trafficking to the cell surface by exploiting the KDEL-receptor recycling pathway. Our recent investigations of CPXV203 reveal that it binds a diverse array of classical and non-classical MHCI proteins with dramatically increased affinities at the lower pH of the Golgi relative to the ER, thereby providing mechanistic insight into how it works synergistically with KDEL receptors to block MHCI surface expression. The strategy used by cowpox to both limit peptide supply and disrupt trafficking of fully assembled MHCI acts as a dual-edged sword that effectively disables adaptive immune surveillance of infected cells.

  1. HIV-1 Trans Infection of CD4+ T Cells by Professional Antigen Presenting Cells

    Directory of Open Access Journals (Sweden)

    Charles R. Rinaldo

    2013-01-01

    Full Text Available Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes to mediate HIV-1 trans infection of CD4+ T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct, cis infection of either APC or T cells, or trans infection between T cells. Such APC-to-T cell trans infection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of these trans infection processes and their role in natural HIV-1 infection.

  2. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation.

    Science.gov (United States)

    Goto, Yoshiyuki; Panea, Casandra; Nakato, Gaku; Cebula, Anna; Lee, Carolyn; Diez, Marta Galan; Laufer, Terri M; Ignatowicz, Leszek; Ivanov, Ivaylo I

    2014-04-17

    How commensal microbiota contributes to immune cell homeostasis at barrier surfaces is poorly understood. Lamina propria (LP) T helper 17 (Th17) cells participate in mucosal protection and are induced by commensal segmented filamentous bacteria (SFB). Here we show that MHCII-dependent antigen presentation of SFB antigens by intestinal dendritic cells (DCs) is crucial for Th17 cell induction. Expression of MHCII on CD11c(+) cells was necessary and sufficient for SFB-induced Th17 cell differentiation. Most SFB-induced Th17 cells recognized SFB in an MHCII-dependent manner. SFB primed and induced Th17 cells locally in the LP and Th17 cell induction occurred normally in mice lacking secondary lymphoid organs. The importance of other innate cells was unveiled by the finding that MHCII deficiency in group 3 innate lymphoid cells (ILCs) resulted in an increase in SFB-independent Th17 cell differentiation. Our results outline the complex role of DCs and ILCs in the regulation of intestinal Th17 cell homeostasis.

  3. Engineered Hydrogen-Bonded Glycopolymer Capsules and Their Interactions with Antigen Presenting Cells.

    Science.gov (United States)

    Kempe, Kristian; Xiang, Sue D; Wilson, Paul; Rahim, Md Arifur; Ju, Yi; Whittaker, Michael R; Haddleton, David M; Plebanski, Magdalena; Caruso, Frank; Davis, Thomas P

    2017-02-22

    Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Multilayer assembly of the hydrogen-bonding pair (glycopolymer/poly(methacrylic acid) (PMA)) onto planar and particulate supports (SiO2 particles, d = 1.16 μm) yielded stable glycopolymer films upon cross-linking by CuAAC. The silica (SiO2) particle templates were removed yielding hollow monodisperse capsules, as demonstrated by fluorescence and scanning electron microscopy. Cellular uptake studies using flow cytometry revealed the preferential uptake of the capsules by DCs when compared to MACs or MDSCs. Mannosylated capsules showed a cytokine independent cis-upregulation of CD80 specifically on DCs and a trans-downregulation of PDL-1 on MDSCs. Thus, the glycopolymer capsules may have potential as vaccine carriers, as they are able to upregulate costimulatory molecules for immune cell stimulation on DCs and at the same time downregulate immune inhibitory receptors on suppressor APC such as MDSCs.

  4. Regulation of Hemichannels and Gap Junction Channels by Cytokines in Antigen-Presenting Cells

    Directory of Open Access Journals (Sweden)

    Pablo J. Sáez

    2014-01-01

    Full Text Available Autocrine and paracrine signals coordinate responses of several cell types of the immune system that provide efficient protection against different challenges. Antigen-presenting cells (APCs coordinate activation of this system via homocellular and heterocellular interactions. Cytokines constitute chemical intercellular signals among immune cells and might promote pro- or anti-inflammatory effects. During the last two decades, two membrane pathways for intercellular communication have been demonstrated in cells of the immune system. They are called hemichannels (HCs and gap junction channels (GJCs and provide new insights into the mechanisms of the orchestrated response of immune cells. GJCs and HCs are permeable to ions and small molecules, including signaling molecules. The direct intercellular transfer between contacting cells can be mediated by GJCs, whereas the release to or uptake from the extracellular milieu can be mediated by HCs. GJCs and HCs can be constituted by two protein families: connexins (Cxs or pannexins (Panxs, which are present in almost all APCs, being Cx43 and Panx1 the most ubiquitous members of each protein family. In this review, we focus on the effects of different cytokines on the intercellular communication mediated by HCs and GJCs in APCs and their impact on purinergic signaling.

  5. Interview: glycolipid antigen presentation by CD1d and the therapeutic potential of NKT cell activation.

    Science.gov (United States)

    Kronenberg, Mitchell

    2007-01-01

    Natural Killer T cells (NKT) are critical determinants of the immune response to cancer, regulation of autioimmune disease, clearance of infectious agents, and the development of artheriosclerotic plaques. In this interview, Mitch Kronenberg discusses his laboratory's efforts to understand the mechanism through which NKT cells are activated by glycolipid antigens. Central to these studies is CD1d--the antigen presenting molecule that presents glycolipids to NKT cells. The advent of CD1d tetramer technology, a technique developed by the Kronenberg lab, is critical for the sorting and identification of subsets of specific glycolipid-reactive T cells. Mitch explains how glycolipid agonists are being used as therapeutic agents to activate NKT cells in cancer patients and how CD1d tetramers can be used to assess the state of the NKT cell population in vivo following glycolipid agonist therapy. Current status of ongoing clinical trials using these agonists are discussed as well as Mitch's prediction for areas in the field of immunology that will have emerging importance in the near future.

  6. Interaction between antigen presenting cells and autoreactive T cells derived from BXSB mice with murine lupus

    Institute of Scientific and Technical Information of China (English)

    Peng Yang; Bo Li; Ping Lv; Yan Zhang; XiaoMing Gao

    2007-01-01

    Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactive T cell (ATL1) clone obtained from lupus-prone BXSB mice. ATL1 cells, either before or after γ-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) were much more powerful stimulators for ATL1 cells on a per cell basis. The T cell stimulating ability of macrophages and B cells, but not DCs, was sensitive toγ-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱand CD4 were able to block DC-mediated stimulation of ATL1 proliferation, indicating cognate recognition between ATL1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.

  7. Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Daniela Cerny

    2014-12-01

    Full Text Available Dengue is a growing global concern with 390 million people infected each year. Dengue virus (DENV is transmitted by mosquitoes, thus host cells in the skin are the first point of contact with the virus. Human skin contains several populations of antigen-presenting cells which could drive the immune response to DENV in vivo: epidermal Langerhans cells (LCs, three populations of dermal dendritic cells (DCs, and macrophages. Using samples of normal human skin we detected productive infection of CD14(+ and CD1c(+ DCs, LCs and dermal macrophages, which was independent of DC-SIGN expression. LCs produced the highest viral titers and were less sensitive to IFN-β. Nanostring gene expression data showed significant up-regulation of IFN-β, STAT-1 and CCL5 upon viral exposure in susceptible DC populations. In mice infected intra-dermally with DENV we detected parallel populations of infected DCs originating from the dermis and migrating to the skin-draining lymph nodes. Therefore dermal DCs may simultaneously facilitate systemic spread of DENV and initiate the adaptive anti-viral immune response.

  8. MHC-restricted antigen presentation and recognition: constraints on gene, recombinant and peptide vaccines in humans

    Directory of Open Access Journals (Sweden)

    Cunha-Neto E.

    1999-01-01

    Full Text Available The target of any immunization is to activate and expand lymphocyte clones with the desired recognition specificity and the necessary effector functions. In gene, recombinant and peptide vaccines, the immunogen is a single protein or a small assembly of epitopes from antigenic proteins. Since most immune responses against protein and peptide antigens are T-cell dependent, the molecular target of such vaccines is to generate at least 50-100 complexes between MHC molecule and the antigenic peptide per antigen-presenting cell, sensitizing a T cell population of appropriate clonal size and effector characteristics. Thus, the immunobiology of antigen recognition by T cells must be taken into account when designing new generation peptide- or gene-based vaccines. Since T cell recognition is MHC-restricted, and given the wide polymorphism of the different MHC molecules, distinct epitopes may be recognized by different individuals in the population. Therefore, the issue of whether immunization will be effective in inducing a protective immune response, covering the entire target population, becomes an important question. Many pathogens have evolved molecular mechanisms to escape recognition by the immune system by variation of antigenic protein sequences. In this short review, we will discuss the several concepts related to selection of amino acid sequences to be included in DNA and peptide vaccines.

  9. 78 FR 14015 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Powered Patient Transport

    Science.gov (United States)

    2013-03-04

    ... Notification; Class II Devices; Powered Patient Transport AGENCY: Food and Drug Administration, HHS. ACTION... requesting exemption from premarket notification requirements for powered patient transport devices commonly... FDA's powered patient transport regulations, including attendant-operated portable...

  10. N-Sulfonyl hydroxamate derivatives as inhibitors of class II fructose-1,6-diphosphate aldolase.

    Science.gov (United States)

    Gavalda, Sabine; Braga, Rémi; Dax, Chantal; Vigroux, Alain; Blonski, Casimir

    2005-12-15

    Dihydroxyacetone-phosphate and phosphonate derivatives were synthesized bearing a N-sulfonyl hydroxamate moiety. The phosphate derivatives represent competitive inhibitors for the class II-FBP aldolase catalyzed reaction, while the phosphonate isosteres are comparatively weaker inhibitors.

  11. 40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

    Science.gov (United States)

    2010-07-01

    ... facility; (vii) Dated records of the quantity (in kilograms) of raw materials and feedstock chemicals used...) Recordkeeping and reporting. Any person who produces, imports, exports, transforms, or destroys class II... total of expended and unexpended production allowances, consumption allowances, export...

  12. Correction of an adult Class II division 2 individual using fixed functional appliance: A noncompliance approach

    Directory of Open Access Journals (Sweden)

    Shrinivas Basavaraddi

    2016-01-01

    Full Text Available This case report describes the application of fixed functional appliance in the treatment of an adult female having Class II division 2 malocclusion with retroclination of upper incisors. Fixed functional appliance was used to correct the overjet after the uprighting of upper incisors. Fixed functional appliance was fitted on a rigid rectangular arch wire. Application of fixed functional appliance achieved a good Class I molar relationship along with Class I canine relationship with normal overjet and overbite. Fixed functional appliance is effective in the treatment of Class II malocclusions, even in adult patients, and can serve as an alternate choice of treatment instead of orthognathic surgery. This is a case; wherein, fixed functional appliance was successfully used to relieve deep bite and overjet that was ensued after leveling and aligning. We demonstrate that fixed functional appliance can act as a “noncompliant corrector” and use of Class II elastics can be avoided.

  13. Stability of class II subdivision malocclusion treatment with 3 and 4 premolar extractions

    OpenAIRE

    2014-01-01

    Background The purpose of this study was to compare the occlusal stability of class II subdivision malocclusion treatment with 3 and 4 first premolar extractions. A sample of 156 dental casts from 52 patients with class II subdivision malocclusion was divided into two groups according to the extraction protocol. Group 1 comprised 24 patients treated with 3 premolar extractions and group 2 included 28 patients treated with 4 premolar extractions. Methods Peer assessment rating (PAR) indexes we...

  14. Marginal and internal adaptation of class II restorations after immediate or delayed composite placement

    OpenAIRE

    Dietschi, Didier; Monasevic, Manuela; Krejci, Ivo; Davidson, Carel

    2002-01-01

    Direct class II composite restorations still represent a challenge, particularly when proximal limits extend below the CEJ. The aim of this in vitro study was to evaluate the influence of the type of adhesive and the delay between adhesive placement and composite insertion on restoration adaptation. Direct class II MOD box-shaped composite restorations (n=8 per group) were placed on intact human third molars, with proximal margins 1mm above or under CEJ. All cavities were filled with a horizo...

  15. Use of cyanoacrylate as barrier in guided tissue regeneration in class II furcation defects

    OpenAIRE

    Carmen L Mueller Storrer; Gabriela dos Santos Kummer; Shaban Mirco; Joao Cesar Zielak

    2014-01-01

    The guided bone regeneration (GBR) is a technique that uses resorbable and non-resorbable membranes in association with other filling biomaterials. GBR is one of the optional treatments for therapy of class II furcation defects. The current case report evaluates clinically and radiographically the use of the cyanoacrylate membrane (Glubran ®2) associated with organic bovine bone (GenOx) for the treatment of vestibular class II furcation defect on the lower left molar. Conclusion: The GBR is a...

  16. The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts

    OpenAIRE

    1996-01-01

    The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules nd lysosomal hydrolases were studied in I-Cell Disease (ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC class II- invariant chain complexes colocalized with the lysosomal hydrolase cathepsin D in buds and vesicles that lacked markers of clathrin-coated vesicle-mediated transport. ...

  17. Oral Impacts on Quality of Life in Adult Patients with Class I, II and III Malocclusion

    OpenAIRE

    Javed, Omair; Bernabé, Eduardo

    2016-01-01

    PURPOSE: To compare the social impact of malocclusion on quality of life between adult patients with Angle Class I, II and III malocclusion.MATERIALS AND METHODS: A total of 222 adult patients (139, 42 and 41 with Angle Class I, II and III malocclusion, respectively) were recruited voluntarily from those attending the Orthodontic Clinic of Khyber College of Dentistry in Pesh awar, Pakistan. Participants were asked to complete the Urdu version of the short form of the Oral Health Impact Profil...

  18. Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules

    Science.gov (United States)

    2011-01-20

    Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules Teri L. Kissner, Gordon Ruthel, Shahabuddin Alam...mediated signaling, which activates pro-inflammatory cytokine responses. Recently we reported that staphylococcal enterotoxins (SEA or SEB), which...upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules. PLoS ONE 6(1): e15985. doi:10.1371/journal.pone.0015985 Editor: Jacques Zimmer

  19. Evaluation and Comparison of Intermaxillary Tooth Size Discrepancy among Class I, Class II Division 1, and Class III Subjects Using Bolton’s Analysis: An in vitro Study

    OpenAIRE

    Prasanna, A Lakshmi; Venkatramana, V; Aryasri, A Srikanth; Katta, Anil Kumar; K. Santhanakrishnan; Maheshwari, Uma

    2015-01-01

    Aim: The aim of the present study was to evaluation and comparison of intermaxillary tooth size discrepancy among Class I, Class II division 1, and Class III subjects using Bolton’s analysis. Materials and Methods: The pre-treatment casts were selected from the records of patients attending the Department of Orthodontics of Meenakshi Ammal Dental College, Chennai. The sample consists of 180 pre-treatment casts with both sexes evenly distributed with 60 casts in each type of malocclusion, i.e....

  20. Class II genes of miniature swine. II. Molecular identification and characterization of B (beta) genes from the SLAc haplotype.

    Science.gov (United States)

    Pratt, K; Sachs, D H; Germana, S; el-Gamil, M; Hirsch, F; Gustafsson, K; LeGuern, C

    1990-01-01

    Genomic clones corresponding to class II beta genes of the SLAc haplotype of miniature swine have been isolated and characterized. These genes have been grouped into seven non-overlapping clusters on the basis of restriction mapping. Ordering of exons within each cluster was accomplished by hybridization of Southern blots of restriction fragments with exon-specific probes. The two clusters (clusters 2 and 3) encoding the DRB and DQB genes were identified on the basis of hybridization with locus-specific 3' untranslated cDNA probes. Cluster 4 contained exons of both DOB and DQB genes, the basis for which remains to be determined. The remaining four clusters (1, 5, 6, 7) were identified as containing DP, DR, and DO coding sequences, respectively, on the basis of sequence analysis. The porcine class II region appears very similar to that of man in number and nature of the class II genes identified and in the intron/exon organization of corresponding genes.

  1. Discovery of Two New Class II Methanol Maser Transitions in G345.01+1.79

    CERN Document Server

    Ellingsen, S P; Cragg, D M; Godfrey, P D

    2012-01-01

    We have used the Swedish ESO Submillimetre Telescope (SEST) to search for new class II methanol maser transitions towards the southern source G345.01+1.79. Over a period of 5 days we observed 11 known or predicted class II methanol maser transitions. Emission with the narrow line width and characteristic velocity of class II methanol masers (in this source) was detected in 8 of these transitions, two of which have not previously been reported as masers. The new class II methanol maser transitions are the 13(-3)-12(-4)E transition at 104.1 GHz and the 5(1)-4(2)E transition at 216.9 GHz. Both of these are from transition series for which there are no previous known class II methanol maser transitions. This takes the total number of known class II methanol maser series to 10, and the total number of transitions (or transition groups) to 18. The observed 104.1 GHz maser suggests the presence of two or more regions of masing gas with similar line of sight velocities, but quite different physical conditions. Althou...

  2. Factors affecting buccal corridor space in Angle′s Class II Division 1 malocclusion

    Directory of Open Access Journals (Sweden)

    Rashmi Bhat

    2014-01-01

    Full Text Available Background and Objectives: Buccal corridor space has been thought of primarily in terms of maxillary width, but there is also evidence that they are heavily influenced by the antero-posterior position of maxilla. The present study was undertaken with an aim of evaluating and comparing the dental and skeletal factors related to buccal corridor space in individuals having Class I and Class II Division 1 malocclusions. Materials and Methods: A total of 80 subjects of which 40 were males and 40 were females in the age group of 20-30 years were selected as per inclusion criteria and were grouped as Group I having Class I malocclusion and as Group II having Class II malocclusions based on angle ANB. 12 linear and 2 angular cephalometric measurements and 4 study cast measurements were used to correlate with the buccal corridor linear ratio (BCLR, calculated on smile photograph using the Adobe Photoshop 7.0 software (Adobe Systems Inc., San Jose, California, USA. The data obtained was statistically evaluated using independent t-test and multiple linear regression analysis. Result: Buccal corridor space is larger in individuals with Class II Division 1 malocclusion when compared with individuals with Class I malocclusions. There exists a significant difference in buccal corridor space between males and females. Conclusion: The present study helps in establishing the correlation between certain factors and the amount of buccal corridor space in individuals having skeletal Class II pattern.

  3. Homing of antigen-presenting cells (APCs in head kidney and spleen – salmon head kidney hosts diverse APC types

    Directory of Open Access Journals (Sweden)

    Dimitar Borisov Iliev

    2013-06-01

    Full Text Available Lymph nodes and spleen are major organs where mammalian APCs initiate and orchestrate Ag-specific immune responses. Unlike mammals, teleosts lack lymph nodes and an interesting question is whether alternative organs may serve as sites for antigen presentation in teleosts. In the current study, fluorescent ovalbumin (Ova and CpG oligonucleotides (ODNs injected intra-abdominally were detected in significant numbers of salmon head kidney (HK MHCII+ cells over a period of 2 weeks while in spleen the percentage of these was transient and declined from day 1 post injection. In vitro studies further shed light on the properties of the diverse MHCII+ cell types found in HK. The ultrastructure of a subpopulation of MHCII+ cells with a high capacity to endocytose and process Ova indicated that these were able to perform constitutive macropinocytosis. Upon stimulation with CpG ODNs these cells upregulated CD86 and gave very high levels of TNF mRNA indicating that these are professional APCs, related to macrophages and dendritic cells (DCs. A subpopulation of HK granulocytes expressed high levels of surface MHCII and upon CpG stimulation upregulated most of the tested APC marker genes. Although these granulocytes expressed TNF weakly, they had relatively high basal levels of IL-1β mRNA and the CpG stimulation upregulated IL-1β, along with its signaling and decoy receptors, to the highest levels as compared to other HK cell types. Interestingly, the high expression of IL-1β mRNA in the granulocytes correlated with a high autophagy flux as demonstrated by LC3-II conversion. Autophagy has recently been found to be implicated in IL-1β processing and secretion and the presented data suggests that granulocytes of salmon, and perhaps other teleost species, may serve as a valuable model to study the involvement of autophagy in regulation of the vertebrate immune response.

  4. Light-induced activation of class II cyclobutane pyrimidine dimer photolyases.

    Science.gov (United States)

    Okafuji, Asako; Biskup, Till; Hitomi, Kenichi; Getzoff, Elizabeth D; Kaiser, Gebhard; Batschauer, Alfred; Bacher, Adelbert; Hidema, Jun; Teranishi, Mika; Yamamoto, Kazuo; Schleicher, Erik; Weber, Stefan

    2010-05-04

    Light-induced activation of class II cyclobutane pyrimidine dimer (CPD) photolyases of Arabidopsis thaliana and Oryza sativa has been examined by UV/Vis and pulsed Davies-type electron-nuclear double resonance (ENDOR) spectroscopy, and the results compared with structure-known class I enzymes, CPD photolyase and (6-4) photolyase. By ENDOR spectroscopy, the local environment of the flavin adenine dinucleotide (FAD) cofactor is probed by virtue of proton hyperfine couplings that report on the electron-spin density at the positions of magnetic nuclei. Despite the amino-acid sequence dissimilarity as compared to class I enzymes, the results indicate similar binding motifs for FAD in the class II photolyases. Furthermore, the photoreduction kinetics starting from the FAD cofactor in the fully oxidized redox state, FAD(ox), have been probed by UV/Vis spectroscopy. In Escherichia coli (class I) CPD photolyase, light-induced generation of FADH from FAD(ox), and subsequently FADH(-) from FADH, proceeds in a step-wise fashion via a chain of tryptophan residues. These tryptophans are well conserved among the sequences and within all known structures of class I photolyases, but completely lacking from the equivalent positions of class II photolyase sequences. Nevertheless, class II photolyases show photoreduction kinetics similar to those of the class I enzymes. We propose that a different, but also effective, electron-transfer cascade is conserved among the class II photolyases. The existence of such electron transfer pathways is supported by the observation that the catalytically active fully reduced flavin state obtained by photoreduction is maintained even under oxidative conditions in all three classes of enzymes studied in this contribution.

  5. Major histocompatibility complex class II compatibility, but not class I, predicts mate choice in a bird with highly developed olfaction.

    Science.gov (United States)

    Strandh, Maria; Westerdahl, Helena; Pontarp, Mikael; Canbäck, Björn; Dubois, Marie-Pierre; Miquel, Christian; Taberlet, Pierre; Bonadonna, Francesco

    2012-11-01

    Mate choice for major histocompatibility complex (MHC) compatibility has been found in several taxa, although rarely in birds. MHC is a crucial component in adaptive immunity and by choosing an MHC-dissimilar partner, heterozygosity and potentially broad pathogen resistance is maximized in the offspring. The MHC genotype influences odour cues and preferences in mammals and fish and hence olfactory-based mate choice can occur. We tested whether blue petrels, Halobaena caerulea, choose partners based on MHC compatibility. This bird is long-lived, monogamous and can discriminate between individual odours using olfaction, which makes it exceptionally well suited for this analysis. We screened MHC class I and II B alleles in blue petrels using 454-pyrosequencing and quantified the phylogenetic, functional and allele-sharing similarity between individuals. Partners were functionally more dissimilar at the MHC class II B loci than expected from random mating (p = 0.033), whereas there was no such difference at the MHC class I loci. Phylogenetic and non-sequence-based MHC allele-sharing measures detected no MHC dissimilarity between partners for either MHC class I or II B. Our study provides evidence of mate choice for MHC compatibility in a bird with a high dependency on odour cues, suggesting that MHC odour-mediated mate choice occurs in birds.

  6. Identification of MHC class II restricted T‐cell‐mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides

    DEFF Research Database (Denmark)

    Wang, Mingjun; Tang, Sheila Tuyet; Stryhn, Anette;

    2011-01-01

    Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide...... blocking with HLA class I and II subtype antibodies in the ELISPOT assay culture, none of the eight antigenic peptides induced HLA class I restricted CD8+ T‐cell responses. Instead all responses were blocked by pan‐HLA class II and anti‐HLA‐DR antibodies. In addition, CD4+ T‐cell depletion before the 10......‐cell immunity against HLA‐I binding 9mer M. tuberculosis‐derived peptides might in many cases turn out to be mediated by CD4+ T cells and restricted by HLA‐II molecules. The use of 9mer peptides recognized by both CD8+ and CD4+ T cells might be of importance for the development of future M. tuberculosis peptide...

  7. A novel laser vaccine adjuvant increases the motility of antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Xinyuan Chen

    Full Text Available BACKGROUND: Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research. METHODOLOGY/PRINCIPAL FINDINGS: We found that laser at a specific setting increased the motility of antigen presenting cells (APCs and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive, 532 nm green laser prior to intradermal (i.d. or intramuscular (i.m. administration of vaccines at the site of laser illumination. The pre-illumination accelerated the motility of APCs as shown by intravital confocal microscopy, leading to sufficient antigen (Ag-uptake at the site of vaccine injection and transportation of the Ag-captured APCs to the draining lymph nodes. As a result, the number of Ag(+ dendritic cells (DCs in draining lymph nodes was significantly higher in both the 1° and 2° draining lymph nodes in the presence than in the absence of LVA. Laser-mediated increases in the motility and lymphatic transportation of APCs augmented significantly humoral immune responses directed against a model vaccine ovalbumin (OVA or influenza vaccine i.d. injected in both primary and booster vaccinations as compared to the vaccine itself. Strikingly, when the laser was delivered by a hair-like diffusing optical fiber into muscle, laser illumination greatly boosted not only humoral but also cell-mediated immune responses provoked by i.m. immunization with OVA relative to OVA alone. CONCLUSION/SIGNIFICANCE: The results demonstrate the ability of this safe LVA to augment both humoral and cell-mediated immune responses. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is novel in both its form and mechanism; it is risk-free and has distinct advantages over traditional vaccine adjuvants.

  8. "Danger" conditions increase sulfamethoxazole-protein adduct formation in human antigen-presenting cells.

    Science.gov (United States)

    Lavergne, S N; Wang, H; Callan, H E; Park, B K; Naisbitt, D J

    2009-11-01

    Antigen-presenting cells (APC) are thought to play an important role in the pathogenesis of drug-induced immune reactions. Various pathological factors can activate APC and therefore influence the immune equilibrium. It is interesting that several diseases have been associated with an increased rate of drug allergy. The aim of this project was to evaluate the impact of such "danger signals" on sulfamethoxazole (SMX) metabolism in human APC (peripheral blood mononuclear cells, Epstein-Barr virus-modified B lymphocytes, monocyte-derived dendritic cells, and two cell lines). APC were incubated with SMX (100 microM-2 mM; 5 min-24 h), in the presence of pathological factors: bacterial endotoxins (lipopolysaccharide and staphylococcal enterotoxin B), flu viral proteins, cytokines [interleukin (IL)-1beta, IL-6, IL-10; tumor necrosis factor-alpha; interferon-gamma; and transforming growth factor-beta], inflammatory molecules (prostaglandin E2, human serum complement, and activated protein C), oxidants (buthionine sulfoximine and H(2)O(2)), and hyperthermia (37.5-39.5 degrees C). Adduct formation was evaluated by enzyme-linked immunosorbent assay and confocal microscopy. SMX-protein adduct formation was time- and concentration-dependent for each cell type tested, in both physiological and danger conditions. A danger environment significantly increased the formation of SMX-protein adducts and significantly shortened the delay for their detection. An additive effect was observed with a combination of danger signals. Dimedone (chemical selectively binding cysteine sulfenic acid) and antioxidants decreased both baseline and danger-enhanced SMX-adduct formation. Various enzyme inhibitors were associated with a significant decrease in SMX-adduct levels, with a pattern varying depending on the cell type and the culture conditions. These results illustrate that danger signals enhance the formation of intracellular SMX-protein adducts in human APC. These findings might be relevant

  9. Modes of salmonid MHC class I and II evolution differ from the primate paradigm

    NARCIS (Netherlands)

    Shum, B.P.; Guethlein, L.; Flodin, L.R.; Adkison, M.A.; Hedrick, R.P.; Nehring, R.B.; Stet, R.J.M.; Secombes, C.; Parham, P.

    2001-01-01

    Rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) represent two salmonid genera separated for 15-20 million years. cDNA sequences were determined for the classical MHC class I heavy chain gene UBA and the MHC class II β-chain gene DAB from 15 rainbow and 10 brown trout. Both genes a

  10. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P

    1991-01-01

    adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human......, but not the class I-negative parental line, 221, showed homotypic aggregation in response to an HLA-G specific mAb (87G) and a broad reacting class I-specific mAb (IOT2). Both cell lines responded with aggregation to anti-class II mAb (TU35). The anti-class I mAb, W6/32, had no effect on all cell lines tested...... and two anti-beta 2-microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature-sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase...

  11. Do orthodontists recommend Class II treatment according to evidence-based knowledge?

    Directory of Open Access Journals (Sweden)

    Soraia Azevedo Almeida

    Full Text Available AbstractIntroductionThe adequate indications for the timing of treatment for Class II malocclusion are mandatory for the ethical and efficient practice of orthodontics, but clinicians are reluctant to accept new information that contradicts their preferred method of treatment.ObjectiveThe aim of this investigation was to assess the agreement regarding the indications for Class II malocclusion interceptive therapy between a group of international opinion-makers on early treatment and a group of orthodontists and to compare their treatment indications with the current evidence-based knowledge.Material and methodAn electronic survey containing photographs of mild, moderate and severe Class II malocclusions in children was sent to two panels of experts. Panel 1 (n=28 was composed of international orthodontists who had authored world-class publications on early orthodontic treatment, and Panel 2 (n=261 was composed of clinical orthodontists. Based on a 5-point Likert-type scale, the orthodontists selected their therapy option for each of the 9 Class II malocclusion cases.ResultThe Class II malocclusion treatment recommendations of Panel 2 were significantly different from those offered by Panel 1 with a skew of at least 1 scale point toward earlier treatment. The Class II malocclusion treatment recommendations of the members of Panel 1 members were in accordance with contemporary evidence-based knowledge.ConclusionClass II malocclusion overtreatment appears to be the tendency among clinical orthodontists but not among orthodontists who are academically involved with early treatment. There is a gap between the scientific knowledge and the practices of orthodontists.

  12. Re-directing CD4+ T cell responses with the flanking residues of MHC class II-bound peptides: the core is not enough

    Directory of Open Access Journals (Sweden)

    David Kenneth Cole

    2013-07-01

    Full Text Available Recombinant αβ T cell receptors (TCRs recognise short peptides presented at the cell surface in complex with MHC molecules. There are two main subsets of αβ T cells: CD8+ T cells that recognise mainly cytosol-derived peptides in the context of MHC class I (pMHC-I, and CD4+ T cells that recognise peptides usually derived from exogenous proteins presented by MHC class II (pMHC-II. Unlike the more uniform peptide lengths (usually 8-13mers bound in the MHC-I closed groove, MHC-II presented peptides are of a highly variable length. The bound peptides consist of a core bound 9mer (reflecting the binding motif for the particular MHC-II type but with variable peptide flanking residues (PFRs that can extend from both the N- and C-terminus of the MHC-II binding groove. Although pMHC-I and pMHC-II play a virtually identical role during T cell responses (T cell antigen presentation and are very similar in overall conformation, there exist a number of subtle but important differences that may govern the functional dichotomy observed between CD8+ and CD4+ T cells. Here, we provide an overview of the impact of structural differences between pMHC-I and pMHC-II and the molecular interactions with the TCR including the functional importance of MHC-II peptide flanking residues. We consider how factors such as anatomical location, inflammatory milieu and particular types of APC might, in theory, contribute to the quantitative (i.e. pMHC ligand frequency as well as qualitative (i.e. variable PFR nature of peptide epitopes, and hence offer a means of control and influence of a CD4+ T cell response. Lastly, we review our recent findings showing how modifications to these flanking regions modify CD4+ T cell antigen recognition. These findings may have novel applications for the development of CD4+ T cell peptide vaccines and diagnostics.

  13. Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases.

    Science.gov (United States)

    Arase, Noriko; Arase, Hisashi

    2015-11-01

    The major function of major histocompatibility complex (MHC) class II molecules is the presentation of peptide antigens to helper T cells. However, when misfolded proteins are associated with MHC class II molecules in the endoplasmic reticulum, they are transported to the cell surface by MHC class II molecules without processing to peptides. Of note, misfolded proteins complexed with MHC class II molecules are specifically recognized by autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins rescued from degradation by MHC class II molecules may be recognized as 'neo-self' antigens by the immune system and be involved in the pathogenicity of autoimmune diseases.

  14. Comparison Between the Sonic-Sys System and Inlay in II Class

    OpenAIRE

    Feder, T.; Mierzwinska-Nastalska, E; Adamczyk-Sosinska, E.; Gladkowski, J.; Siedlecki, M.

    2002-01-01

    In everyday dental practice we often face the problem of class II restorations. Large caries create serious problems with regard to obtaining correct contact points, marginal fit (expecially in the gingival area) and good resin polymerisation. In such cases usage of the Sonic-Sys system and inlays seems to be the best solution. The aim of this poster is to present a manual of the Sonic-Sys system, as well as comparison of the Empress II and Sonic-Sys system inlays in class II restorations....

  15. Management of severe Class II malocclusion with sequential modified twin block and fixed orthodontic appliances

    Directory of Open Access Journals (Sweden)

    Sonal Chowdhary

    2016-01-01

    Full Text Available Functional appliance is an effective way of treating skeletal Class II malocclusion in children and adolescents. A 12 months stepwise mandibular advancement protocol with Herbst appliance has been proved to enhance condylar growth and improve mandibular prognathism. The present case report documents a 12-year-old boy presenting with Angle's Class II, division 1 malocclusion associated with excessive overjet (11 mm, 100% deep bite, and retrognathic mandible. He was treated by a phase I growth modification therapy using twin block appliance with lip pads in a stepwise mandibular advancement protocol followed by a phase II preadjusted Edgewise appliance therapy.

  16. IL-27 in human secondary lymphoid organs attracts myeloid dendritic cells and impairs HLA class I-restricted antigen presentation.

    Science.gov (United States)

    Morandi, Fabio; Di Carlo, Emma; Ferrone, Soldano; Petretto, Andrea; Pistoia, Vito; Airoldi, Irma

    2014-03-15

    Different cytokines play crucial roles in inflammation and in polarizing immune responses, including IL-27 that exerts pro- and anti-inflammatory functions. Although the activity of IL-27 is well characterized in murine immune cells, only limited information is available regarding the natural cellular sources of IL-27 in humans and its effects on human immune cells. Dendritic cells (DCs) are the most potent professional APCs that in the immature state are positioned throughout peripheral tissues by acting as sentinels, sensing the presence of Ags. Activated DCs migrate into the lymph nodes and direct Ag-specific T cell responses, thus acting as key players in both adaptive and innate immunity. In this study we asked whether IL-27 is produced by human secondary lymphoid organs and what is its functional role on human DCs. To our knowledge, we provide the first evidence that 1) in lymph nodes, macrophages are the major source for IL-27; 2) immature and mature human DCs express functional IL-27R; 3) IL-27 exerts immunosuppressive activity by crippling the Ag processing machinery in immature DCs under steady-state conditions and after pulsing with a viral Ag; and 4) IL-27 is chemotactic for human DCs. Our findings highlight novel mechanisms underlying the immunosuppressive activity of IL-27, suggesting that this cytokine may function as a homeostatic cytokine in secondary lymphoid organs by limiting duration and/or intensity of ongoing adaptive immune responses. The results presented in this study pave the way to future studies aimed at investigating whether dysregulation of IL-27 expression and function may be involved in pathogenesis of autoimmune disease and cancer.

  17. Successful treatment of Class II malocclusion with bidental protrusion using standard edgewise prescription

    Directory of Open Access Journals (Sweden)

    Mohd Ayaz

    2016-01-01

    Full Text Available This case report deals with the successful orthodontic treatment of a 14-year-old female patient having Class II malocclusion with bidental protrusion using standard edgewise prescription. She reported with forwardly placed upper front teeth and difficulty in closing lips. She had prognathic maxilla, retrognathic mandible, and full cusp Class II molar and canine relation bilaterally with overjet of 7 mm. She was in cervical vertebrae maturation indicator Stage IV. The case was treated by fixed extraction mechanotherapy. Interarch Class II mechanics was used to retract the upper incisor and to mesialize the lower molars. Simultaneously, Class I mechanics was used to upright lower incisors. Tip back bend, curve of Spee, and extra palatal root torque were incorporated in upper archwire to maintain molars in upright position and prevent extrusion and deepening of bite, respectively. There was satisfactory improvement in facial profile at the end of 24 months. After a follow-up of 6 months, occlusion was stable.

  18. Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides

    DEFF Research Database (Denmark)

    Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren;

    2016-01-01

    The aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02......:01 and HLA-DRB1*01:01 molecules were identified by bioinformatics and biochemical technology. Immunization of transgenic HLA-A*02:01/HLA-DRB1*01:01 mice with four of these double binding peptides gave rise to both HLA class I and class II restricted responses by CD8 and CD4 T cells, respectively, whereas...... with this, peptide vaccination did not decrease virus titres in the lungs of intranasally influenza challenged mice. Our data show that HLA class I and class II double binding peptides can be identified by bioinformatics and biochemical technology. By immunization, double binding peptides can give rise...

  19. Vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells.

    Science.gov (United States)

    Deng, Liang; Dai, Peihong; Ding, Wanhong; Granstein, Richard D; Shuman, Stewart

    2006-10-01

    Langerhans cells (LCs) are antigen-presenting cells in the skin that play sentinel roles in host immune defense by secreting proinflammatory molecules and activating T cells. Here we studied the interaction of vaccinia virus with XS52 cells, a murine epidermis-derived dendritic cell line that serves as a surrogate model for LCs. We found that vaccinia virus productively infects XS52 cells, yet this infection displays an atypical response to anti-poxvirus agents. Whereas adenosine N1-oxide blocked virus production and viral protein synthesis during a synchronous infection, cytosine arabinoside had no effect at concentrations sufficient to prevent virus replication in BSC40 monkey kidney cells. Vaccinia virus infection of XS52 cells not only failed to elicit the production of various cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-10, IL-12 p40, alpha interferon (IFN-alpha), and IFN-gamma, it actively inhibited the production of proinflammatory cytokines TNF-alpha and IL-6 by XS52 cells in response to exogenous lipopolysaccharide (LPS) or poly(I:C). Infection with a vaccinia virus mutant lacking the E3L gene resulted in TNF-alpha secretion in the absence of applied stimuli. Infection of XS52 cells or BSC40 cells with the DeltaE3L virus, but not wild-type vaccinia virus, triggered proteolytic decay of IkappaBalpha. These results suggest a novel role for the E3L protein as an antagonist of the NF-kappaB signaling pathway. DeltaE3L-infected XS52 cells secreted higher levels of TNF-alpha and IL-6 in response to LPS and poly(I:C) than did cells infected with the wild-type virus. XS52 cells were productively infected by a vaccinia virus mutant lacking the K1L gene. DeltaK1L-infected cells secreted higher levels of TNF-alpha and IL-6 in response to LPS than wild-type virus-infected cells. Vaccinia virus infection of primary LCs harvested from mouse epidermis was nonpermissive, although a viral reporter protein was

  20. Linkage relationships in the bovine MHC region. High recombination frequency between class II subregions.

    Science.gov (United States)

    Andersson, L; Lundén, A; Sigurdardottir, S; Davies, C J; Rask, L

    1988-01-01

    Class II genes of the bovine major histocompatibility complex (MHC) have been investigated by Southern blot analysis using human DNA probes. Previous studies revealed the presence of bovine DO beta, DQ alpha, DQ beta, DR alpha, and DR beta genes, and restriction fragment length polymorphisms for each of these genes were documented. In the present study, the presence of three additional class II genes, designated DZ alpha, DY alpha, and DY beta, are reported. DZ alpha was assumed to correspond to the human DZ alpha gene while the other two were designated DY because their relationship to human class II genes could not be firmly established. The linkage relationships among bovine class II genes and two additional loci, TCP1B and C4, were investigated by family segregation analysis and analysis of linkage disequilibrium. The results clearly indicated that all these loci belong to the same linkage group. This linkage group is divided into two subregions separated by a fairly high recombination frequency. One region includes the C4, DQ alpha, DQ beta, DR alpha, and DR beta loci and the other one is composed of the DO beta, DY alpha, DY beta, and TCP1B loci. No recombinant was observed within any of these subregions and there was a strong or fairly strong linkage disequilibrium between loci within groups. In contrast, as many as five recombinants among three different families were detected in the interval between these subregions giving a recombination frequency estimate of 0.17 +/- 0.07. The fairly high recombination frequency observed between class II genes in cattle is strikingly different from the corresponding recombination estimates in man and mouse. The finding implies either a much larger molecular distance between some of the bovine class II genes or alternatively the presence of a recombinational "hot spot" in the bovine class II region.

  1. Stability of molar relationship after non-extraction Class II malocclusion treatment

    Directory of Open Access Journals (Sweden)

    Darwin Vaz de Lima

    2013-04-01

    Full Text Available OBJECTIVE: This study aimed to evaluate the stability of molar relationship after non-extraction treatment of Class II malocclusion. METHODS: The sample comprised 39 subjects (16 females, 23 males with initial Class II malocclusion treated with no extractions, using fixed appliances. Mean age at the beginning of treatment was 12.94 years, at the end of treatment was 15.14 years and at post-retention stage was 21.18 years. Mean treatment time was 2.19 years and mean time of post-treatment evaluation was 6.12 years. To verify the influence of the severity of initial Class II molar relationship in stability of molar relationship, the sample was divided into two groups, one presenting a ½-cusp or ¾-cusp Class II molar relationship, and the other with full-cusp Class II molar relationship. In dental casts from initial, final and postretention stages, molar, first and second premolars and canine relationships were measured. Data obtained were analyzed by dependent ANOVA, Tukey and Pearson's correlation tests, as well as independent t test between the two groups divided by severity of initial molar relationship. RESULTS: There was a non-statistically significant 0.12 mm relapse of molar relationship. The initial severity of Class II molar relationship was not correlated to relapse in the post-retention period. When compared, the two groups showed no difference in relapse of molar relationship. CONCLUSION: It was concluded that correction of Class II molar relationship is stable and initial severity does not influence relapse of molar relationship.

  2. HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Jesionek-Kupnicka, Dorota; Bojo, Marcin; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna; Jabłońska, Joanna; Kalinka-Warzocha, Ewa; Kordek, Radzisław; Młynarski, Wojciech; Robak, Tadeusz; Warzocha, Krzysztof; Lech-Maranda, Ewa

    2016-06-01

    The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.

  3. Assessment of upper airways measurements in patients with mandibular skeletal Class II malocclusion

    Directory of Open Access Journals (Sweden)

    Nayanna Nadja e Silva

    2015-10-01

    Full Text Available Objective: Mandibular Class II malocclusions seem to interfere in upper airways measurements. The aim of this study was to assess the upper airways measurements of patients with skeletal Class II malocclusion in order to investigate the association between these measurements and the position and length of the mandible as well as mandibular growth trend, comparing the Class II group with a Class I one.Methods:A total of 80 lateral cephalograms from 80 individuals aged between 10 and 17 years old were assessed. Forty radiographs of Class I malocclusion individuals were matched by age with forty radiographs of individuals with mandibular Class II malocclusion. McNamara Jr., Ricketts, Downs and Jarabak's measurements were used for cephalometric evaluation. Data were submitted to descriptive and inferential statistical analysis by means of SPSS 20.0 statistical package. Student's t-test, Pearson correlation and intraclass correlation coefficient were used. A 95% confidence interval and 5% significance level were adopted to interpret the results.Results:There were differences between groups. Oropharynx and nasopharynx sizes as well as mandibular position and length were found to be reduced in Class II individuals. There was a statistically significant positive correlation between the size of the oropharynx and Xi-Pm, Co-Gn and SNB measurements. In addition, the size of the nasopharynx was found to be correlated with Xi-Pm, Co-Gn, facial depth, SNB, facial axis and FMA.Conclusion: Individuals with mandibular Class II malocclusion were shown to have upper airways measurements diminished. There was a correlation between mandibular length and position and the size of oropharynx and nasopharynx.

  4. Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity.

    Science.gov (United States)

    Merelo, Paz; Ram, Hathi; Pia Caggiano, Monica; Ohno, Carolyn; Ott, Felix; Straub, Daniel; Graeff, Moritz; Cho, Seok Keun; Yang, Seong Wook; Wenkel, Stephan; Heisler, Marcus G

    2016-10-18

    A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD-ZIP) transcription factors are key mediators in the regulation of adaxial-abaxial patterning. Their expression is restricted adaxially during early development by the abaxially expressed microRNA (MIR)165/166, yet the mechanism that restricts MIR165/166 expression to abaxial leaf tissues remains unknown. Here, we show that class III and class II HD-ZIP proteins act together to repress MIR165/166 via a conserved cis-element in their promoters. Organ morphology and tissue patterning in plants, therefore, depend on a bidirectional repressive circuit involving a set of miRNAs and its targets.

  5. A Class I and Class II Methanol Maser Survey of Extended Green Objects (EGOs) from the GLIMPSE Survey

    CERN Document Server

    Cyganowski, C J; Hunter, T R; Churchwell, E

    2009-01-01

    We present the results of a high angular resolution Very Large Array (VLA) Class I 44 GHz and Class II 6.7 GHz methanol maser survey of a sample of ~20 massive young stellar object (MYSO) outflow candidates selected on the basis of extended 4.5 micron emission in Spitzer Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE) images. These 4.5 micron-selected candidates are referred to as extended green objects (EGOs), for the common coding of this band as green in three-color IRAC images. The detection rate of 6.7 GHz Class II methanol masers, which are associated exclusively with massive YSOs, towards EGOs is greater than ~64%--nearly double the detection rate of surveys using other MYSO selection criteria. The detection rate of Class I 44 GHz methanol masers, which trace molecular outflows, is ~89% towards EGOs associated with 6.7 GHz methanol masers. The two types of methanol masers exhibit different spatial distributions: 6.7 GHz masers are centrally concentrated and usually coincide with 24 m...

  6. Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101-positive antigen-presenting cells.

    Science.gov (United States)

    Anani Sarab, Gholamreza; Moss, Michael; Barker, Robert N; Urbaniak, Stanislaw J

    2009-08-27

    In neonatal alloimmune thrombocytopenia, almost all human platelet antigen (HPA)-1b1b mothers who produce anti-HPA-1a antibody through carrying an HPA-1a fetus are human histocompatibility leukocyte antigen (HLA)-DRB3*0101 positive. It is predicted that the HPA-1a Leu(33) polymorphism forms part of an HLA-DRB3*0101-restricted T-helper epitope, and acts as an anchor residue for binding this class II molecule. However, it is not known whether any corresponding peptides are naturally processed and presented from platelet glycoprotein. In this study, peptides displayed by a homozygous HLA-DRB3*0101 antigen-presenting cell line were identified after pulsing with recombinant HPA-1a (Leu(33) plexin-semaphorin-integrin domain). The peptides were eluted from HLA-DR molecules, fractionated by high performance liquid chromatography, and analyzed by tandem mass spectrometry. A "nested set" of naturally presented HPA-1a-derived peptides, each containing the Trp(25)-Leu(33) core epitope, was identified, with the most abundant member being the 16-mer Met(22)-Arg(37). These peptides may provide the basis for novel treatments to tolerize the corresponding T-helper response in women at risk of neonatal alloimmune thrombocytopenia.

  7. PowerScope a Class II corrector – A case report

    Directory of Open Access Journals (Sweden)

    Joby Paulose

    2016-01-01

    Full Text Available Managing mild to moderate Class II malocclusion is a one of the common and major challenges to orthodontists. Class II discrepancies with mandibular deficiency during active growth are usually treated by myofunctional appliances. Fixed functional appliances evolved due to the noncompliance with conventional myofunctional appliances. This case report illustrates the efficiency of PowerScope in correction of skeletal Class II with mandibular deficiency in a patient aged 13 years who has reported to the department with a chief complaint of forwardly placed upper front teeth. This case with functional jaw retrusion was treated initially with MBT 0.022” prescription followed by PowerScope. Pre-, mid- and post-treatment cephalograms were obtained, and cephalometric analysis was performed. Stable and successful results were obtained with a substantial improvement in facial profile, skeletal jaw relationship, and overall esthetic appearance of the patient. A significant forward displacement of the mandible was the principal element for successful correction of Class II malocclusion. PowerScope provides the best results for Class II management, thus enables us to treat such cases by a nonextraction approach rather than contemplating extractions.

  8. Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Brisebois, Marcel; Tran, Elise;

    2003-01-01

    It has been proposed that the activation status of antigen-presenting cells (APCs) plays a significant role in the development of autoimmune disease. Whether expression of costimulatory ligands on tissue-resident APCs controls organ-specific autoimmune responses has not been tested. We here repor...... sclerosis (MS) and Guillain-Barré syndrome (GBS)....

  9. Identification of MHC class II restricted T-cell-mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides.

    Science.gov (United States)

    Wang, Mingjun; Tang, Sheila T; Stryhn, Anette; Justesen, Sune; Larsen, Mette V; Dziegiel, Morten H; Lewinsohn, David M; Buus, Søren; Lund, Ole; Claesson, Mogens H

    2011-04-01

    Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide-based vaccines. In the present work, bioinformatics technology was employed to predict binding motifs of 9mer peptides derived from M. tuberculosis for the 12 HLA-I supertypes. Subsequently, the predicted peptides were synthesized and assayed for binding to HLA-I molecules in a biochemically based system. The antigenicity of a total of 157 peptides with measured affinity for HLA-I molecules of K(D) ≤ 500 nM were evaluated using peripheral blood T cells from strongly purified protein derivative reactive healthy donors. Of the 157 peptides, eight peptides (5%) were found to induce T-cell responses. As judged from blocking with HLA class I and II subtype antibodies in the ELISPOT assay culture, none of the eight antigenic peptides induced HLA class I restricted CD8(+) T-cell responses. Instead all responses were blocked by pan-HLA class II and anti-HLA-DR antibodies. In addition, CD4(+) T-cell depletion before the 10 days of expansion, resulted in total loss of reactivity in the ELISPOT culture for most peptide specificities. FACS analyses with intracellular interferon-γ staining of T cells expanded in the presence of M. tuberculosis peptides confirmed that the responsive cells were indeed CD4(+). In conclusion, T-cell immunity against HLA-I binding 9mer M. tuberculosis-derived peptides might in many cases turn out to be mediated by CD4(+) T cells and restricted by HLA-II molecules. The use of 9mer peptides recognized by both CD8(+) and CD4(+) T cells might be of importance for the development of future M. tuberculosis peptide-based vaccines.

  10. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false What are the minimum technical hardware standards applicable to Class II gaming systems? 547.7 Section 547.7 Indians NATIONAL INDIAN GAMING COMMISSION... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class...

  11. Fixed Lingual Mandibular Growth Modificator: a new appliance for Class II correction

    Directory of Open Access Journals (Sweden)

    Osama Hasan Alali

    2013-08-01

    Full Text Available INTRODUCTION: This article demonstrates the description and use of a new appliance for Class II correction. MATERIAL AND METHODS: A case report of a 10-year 5 month-old girl who presented with a skeletally-based Class II division 1 malocclusion (ANB = 6.5º on a slightly low-angle pattern, with ML-NSL angle of 30º and ML-NL angle of 22.5º. Overjet was increased (7 mm and associated with a deep bite. RESULTS: Overjet and overbite reduction was undertaken with the new appliance, Fixed Lingual Mandibular Growth Modificator (FLMGM. CONCLUSION: FLMGM may be effective in stimulating the growth of the mandible and correcting skeletal Class II malocclusions. Clinicians can benefit from the unique clinical advantages that FLMGM provides, such as easy handling and full integration with bracketed appliance at any phase.

  12. Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D.

    Science.gov (United States)

    Coronado, M A; Ullah, A; da Silva, L S; Chaves-Moreira, D; Vuitika, L; Chaim, O M; Veiga, S S; Chahine, J; Murakami, M T; Arni, R K

    2015-01-01

    Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms, trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental in understanding the functional differences between the class I and II spider PLDs. The crystal structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided insights into the structural determinants for substrate recognition and binding by class II PLDs.

  13. Identification of putative cathepsin S in mangrove red snapper Lutjanus argentimaculatus and its role in antigen presentation.

    Science.gov (United States)

    Zhou, Jin; Li, Lei; Cai, Zhong-Hua

    2012-05-01

    Cathepsin S (CTSS) is a key enzyme employed in the histocompatibility complex (MHC) class II-restricted antigens, which are presented by processing class II-associated invariant chains and loaded antigen peptides into class II molecules. To date, little is known about the character and function of CTSS in fish. In the present study, we screened and identified a CTSS cDNA sequence from the mangrove red snapper head kidney cDNA library. The full-length CTSS cDNA contained 1339-bp nucleotide acids encoding 337 amino acids. The sequence shared high identity and similarity with other known cathepsins, especially CTSS (about 56-78% and 79-89%, respectively). Like other cathepsins, the deduced peptide consisted of regions with N-terminal signal peptides, propeptides, and mature peptides. A typical ERWNIN motif in L-like cathepsins and three conservative catalytic activity sites forming a catalytic triad active center were respectively identified in the pro-peptide and mature peptide regions of CTSS. Phylogenetic analysis revealed that mangrove red snapper CTSS was located in the CTSS clade belonging to the L-like cathepsin group, and evolved from the same ancestry. To further characterize the biological activity of the putative CTSS of mangrove snapper, CTSS was expressed in Escherichia coli M15 strains. Like other mammalian CTSS, the recombinant CTSS (rCTSS) had autocatalytic activation properties, can remove pro-peptides, and can release active mature peptides. Active CTSS had the ability to catalyze Z-Phe-Arg-AMC substrates in acidic conditions (pH 5.0) and weak alkaline environments (pH 7.5); this activity could be blocked by the cysteine protease inhibitor E-64. Active CTSS can process recombinant Ii chains (invariant chains) in a stepwise manner in vitro. The results indicate that mangrove red snapper CTSS is a lysosomal cysteine protease family member with a key role in antigen processing in fish.

  14. Exposing the specific roles of the invariant chain isoforms in shaping the MHC class II peptidome

    Directory of Open Access Journals (Sweden)

    Jean-Simon eFortin

    2013-12-01

    Full Text Available The peptide repertoire (peptidome associated with MHC class II molecules (MHCIIs is influenced by the polymorphic nature of the peptide binding groove but also by cell-intrinsic factors. The invariant chain (Ii chaperones MHCIIs, affecting their folding and trafficking. Recent discoveries relating to Ii functions have provided insights as to how it edits the MHCII peptidome. In humans, the Ii gene encodes four different isoforms for which structure-function analyses have highlighted common properties but also some non-redundant roles. Another layer of complexity arises from the fact that Ii heterotrimerizes, a characteristic that has the potential to affect the maturation of associated MHCIIs in many different ways, depending on the isoform combinations. Here, we emphasize the peptide editing properties of Ii and discuss the impact of the various isoforms on the MHCII peptidome.

  15. Exposing the Specific Roles of the Invariant Chain Isoforms in Shaping the MHC Class II Peptidome.

    Science.gov (United States)

    Fortin, Jean-Simon; Cloutier, Maryse; Thibodeau, Jacques

    2013-12-13

    The peptide repertoire (peptidome) associated with MHC class II molecules (MHCIIs) is influenced by the polymorphic nature of the peptide binding groove but also by cell-intrinsic factors. The invariant chain (Ii) chaperones MHCIIs, affecting their folding and trafficking. Recent discoveries relating to Ii functions have provided insights as to how it edits the MHCII peptidome. In humans, the Ii gene encodes four different isoforms for which structure-function analyses have highlighted common properties but also some non-redundant roles. Another layer of complexity arises from the fact that Ii heterotrimerizes, a characteristic that has the potential to affect the maturation of associated MHCIIs in many different ways, depending on the isoform combinations. Here, we emphasize the peptide editing properties of Ii and discuss the impact of the various isoforms on the MHCII peptidome.

  16. High-throughput engineering and analysis of peptide binding to class II MHC.

    Science.gov (United States)

    Jiang, Wei; Boder, Eric T

    2010-07-27

    Class II major histocompatibility complex (MHC-II) proteins govern stimulation of adaptive immunity by presenting antigenic peptides to CD4+ T lymphocytes. Many allelic variants of MHC-II exist with implications in peptide presentation and immunity; thus, high-throughput experimental tools for rapid and quantitative analysis of peptide binding to MHC-II are needed. Here, we present an expression system wherein peptide and MHC-II are codisplayed on the surface of yeast in an intracellular association-dependent manner and assayed by flow cytometry. Accordingly, the relative binding of different peptides and/or MHC-II variants can be assayed by genetically manipulating either partner, enabling the application of directed evolution approaches for high-throughput characterization or engineering. We demonstrate the application of this tool to map the side-chain preference for peptides binding to HLA-DR1 and to evolve novel HLA-DR1 mutants with altered peptide-binding specificity.

  17. The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.

    Science.gov (United States)

    Jones, K; Wockner, L; Brennan, R M; Keane, C; Chattopadhyay, P K; Roederer, M; Price, D A; Cole, D K; Hassan, B; Beck, K; Gottlieb, D; Ritchie, D S; Seymour, J F; Vari, F; Crooks, P; Burrows, S R; Gandhi, M K

    2016-02-01

    In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein-Barr virus (EBV) latency-II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV(+) cHL) in the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA-A*02 is protective in EBV(+) cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL. To ascertain the impact of HLA class I on EBV latency antigen-specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients. Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines. In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02. Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens. Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.

  18. Is traditional treatment a good option for an adult with a Class II deepbite malocclusion?

    Science.gov (United States)

    Abdo Quintão, Catia Cardoso; Miguel, Jose Augusto Mendes; Brunharo, Ione Portela; Zanardi, Gustavo; Feu, Daniela

    2012-01-01

    The Tweed-Merrifield directional force technique is a useful treatment approach for a patient with a Class II malocclusion with dentoalveolar protrusion. The purpose of this case report was to present the diagnosis and treatment descriptions of a patient with an Angle Class II malocclusion complicated by tooth losses, severe dentoalveolar protrusion, and skeletal discrepancy. Treatment involved extraction of the maxillary first premolars, high-pull headgear to enhance anchorage, and high-pull J-hook headgear to retract and intrude the maxillary anterior segments. A successful outcome was achieved with traditional orthodontic treatment in this borderline surgical case.

  19. Limitations of Ab Initio Predictions of Peptide Binding to MHC Class II Molecules

    DEFF Research Database (Denmark)

    Zhang, Hao; Lund, Ole; Nielsen, Morten;

    2010-01-01

    on the highly conserved 3D structure of peptide:MHC complexes. While several such methods have been described before, most are not publicly available and have not been independently tested for their performance. We here implemented and evaluated three prediction methods for MHC class II molecules: statistical...... methods prediction performance showed that these are significantly better than random, but still substantially lower than the best performing sequence based class II prediction methods available. While the approaches presented here were developed independently, we have chosen to present our results...

  20. Vaccination against lymphocytic choriomeningitis virus infection in MHC class II-deficient mice

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2011-01-01

    response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8(+) T cell-mediated protection...... against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4(+) T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute...

  1. HLA class II haplotypes distinctly associated with vaso-occlusion in children with sickle cell disease.

    Science.gov (United States)

    Mahdi, Najat; Al-Ola, Khadija; Al-Subaie, Abeer M; Ali, Muhallab E; Al-Irhayim, Zaid; Al-Irhayim, A Qader; Almawi, Wassim Y

    2008-04-01

    We investigated the association of HLA class II alleles and haplotypes with sickle cell anemia vaso-occlusive crisis (VOC). DRB1*100101 was positively associated, while DRB1*140101, DRB1*150101, and DQB1*060101 were negatively associated, with VOC. Both susceptible (DRB1*100101-DQB1*050101) and protective (DRB1*110101-DQB1*030101 and DRB1*150101-DQB1*060101) haplotypes were identified, indicating that HLA class II haplotypes influence VOC risk.

  2. Domain structures and molecular evolution of class I and class II major histocompatibility gene complex (MHC) products deduced from amino acid and nucleotide sequence homologies.

    Science.gov (United States)

    Ohnishi, K

    1984-01-01

    Domain structures of class I and class II MHC products were analyzed from a viewpoint of amino acid and nucleotide sequence homologies. Alignment statistics revealed that class I (transplantation) antigen H chains consist of four mutually homologous domains, and that class II (HLA-DR) antigen beta and alpha chains are both composed of three mutually homologous ones. The N-terminal three and two domains of class I and class II (both beta and alpha) gene products, respectively, all of which being approximately 90 residues long, were concluded to be homologous to beta2-microglobulin (beta2M). The membrane-embedded C-terminal shorter domains of these MHC products were also found to be homologous to one another and to the third domain of class I H chains. Class I H chains were found to be more closely related to class II alpha chains than to class II beta chains. Based on these findings, an exon duplication history from a common ancestral gene encoding a beta2M-like primodial protein of one-domain-length up to the contemporary MHC products was proposed.

  3. 46 CFR 50.30-10 - Class I, I-L and II-L pressure vessels.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Class I, I-L and II-L pressure vessels. 50.30-10 Section... PROVISIONS Fabrication Inspection § 50.30-10 Class I, I-L and II-L pressure vessels. (a) Classes I, I-L and II-L pressure vessels shall be subject to shop inspection at the plant where they are...

  4. A Review of Class I and Class II Pet Food Recalls Involving Chemical Contaminants from 1996 to 2008

    OpenAIRE

    2010-01-01

    Commercial pet food in USA is generally safe, but adulteration does occur. Adulterated food has to be recalled to protect pets and public health. All stakeholders, including food firms, distributors, and government agencies such as the Food and Drug Administration (FDA) participate in food recall. The objective of this review is to describe the pet food recall procedure from start to finish, and to review class I and II pet food recalls from 1996 to 2008, with a specific focus on those due to...

  5. Juvenile idiopathic arthritis (JIA): a screening study to measure class II skeletal pattern, TMJ PDS and use of systemic corticosteroids.

    LENUS (Irish Health Repository)

    Mandall, Nicky A

    2010-03-01

    To screen patients with oligoarticular and polyarticular forms of Juvenile Idiopathic Arthritis (JIA) to determine (i) the severity of their class II skeletal pattern; (ii) temporomandibular joint signs and symptoms and (iii) use of systemic corticosteroids.

  6. Detection of Rare Antigen Presenting Cells through T cell-intrinsic meandering motility, mediated by Myo1g

    OpenAIRE

    Gérard, Audrey; Patino-Lopez, Genaro; Beemiller, Peter; Nambiar, Rajalakshmi; Ben-Aissa, Khadija; Liu, Yin; Totah, Fadi J.; Tyska, Matthew J.; Shaw, Stephen; Krummel, Matthew F.

    2014-01-01

    To mount an immune response, T lymphocytes must successfully search for foreign material bound to the surface of antigen-presenting cells. How T cells optimize their chances of encountering and responding to these antigens is unknown. T cell motility in tissues resembles a random or Levy walk and is regulated in part by external factors including chemokines and lymph node topology, but motility parameters such as speed and propensity to turn may also be cell-intrinsic. Here we found that the ...

  7. Extraction of maxillary first permanent molars in patients with Class II Division 1 malocclusion.

    NARCIS (Netherlands)

    Stalpers, M.J.; Booij, J.W.; Bronkhorst, E.M.; Kuijpers-Jagtman, A.M.; Katsaros, C.

    2007-01-01

    INTRODUCTION: Our objectives were to assess treatment outcomes in Class II Division 1 patients who were treated orthodontically with extraction of the maxillary first permanent molars and to describe the changes in their facial profiles. METHODS: This was a prospective, longitudinal, 1-group outcome

  8. A treatment method for Class II Division 1 patients with extraction of permanent maxillary first molars.

    NARCIS (Netherlands)

    Booij, J.W.; Kuijpers-Jagtman, A.M.; Katsaros, C.

    2009-01-01

    Throughout the years, various treatment modalities have been presented for the treatment of Class II Division 1 malocclusions. The goal of this paper is to present a treatment approach that involves the extraction of the maxillary first molars followed by use of fixed appliances with low-friction br

  9. MHC class II B diversity in blue tits : A preliminary study

    NARCIS (Netherlands)

    Rivero-de Aguilar, Juan; Schut, Elske; Merino, Santiago; Martinez, Javier; Komdeur, Jan; Westerdahl, Helena

    2013-01-01

    In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were investigate

  10. Very few indications justify early treatment for severe Class II malocclusions

    NARCIS (Netherlands)

    Ren, Yijin

    2004-01-01

    DESIGN: This was a single-centre two-phased, parallel, randomised clinical trial (RCT) conducted over a period of more than 10 years. INTERVENTION: Children were enrolled who had severe (=7 mm overjet) Class II malocclusions and who were developmentally at least a year before their peak pubertal gro

  11. Current Teaching of Proximal Retention Grooves for Class II Amalgam Preparations.

    Science.gov (United States)

    Moore, David L.

    1992-01-01

    A survey gathered information on methods of class II amalgam preparation taught in 59 dental schools. Focus was on the teaching and testing of proximal retention groove use, stated rationale for placing retention grooves, and the relationship of the instruction to board criteria for cavity preparation. (MSE)

  12. The effect of anterior inclined plane treatment on the dentoskeletal of Class II division 1 patients

    Directory of Open Access Journals (Sweden)

    Emami Meibodi

    2007-09-01

    Full Text Available Most of Class II malocclusions are due to underdeveloped mandible with increased overjet and overbite. Lack of incisal contact results in the extrusion of the upper and lower anterior dentoalveolar complex, which helps to lock the mandible and prevent its normal growth and development, and this abnormality is exaggerated by soft tissue imbalance. The purpose of this study was to evaluate the skeletal and dental changes in patients treated with anterior inclined plane appliance in growing patients with moderate Class II Division 1 having deep overbite. In this study, 25 patients, including 15 girls and 10 boys, with a mean age of 9 ±1.2 years were selected; all of them presented with moderate Class II deep bite with increased overjet and normal or horizontal growth pattern. Pre- and post-treatment X-rays and photos for an average of 8 months were taken. The statistical assessment of the data suggested that there were no significant changes in the vertical skeletal parameters. The mandibular incisors were protruded, whereas the maxillary incisors were retruded. Overbite and overjet were also reduced. There was significant increase in the mandibular length. The results revealed that in mixed dentition patients, the inclined plane corrected Class II discrepancies mostly through dentoskeletal changes.

  13. 77 FR 58473 - Minimum Technical Standards for Class II Gaming Systems and Equipment

    Science.gov (United States)

    2012-09-21

    ... supported the NPRM's removal of language asserting that ``TGRAs also regulate Class II gaming,'' but... primary regulators of tribal gaming. Response: The Commission declines to insert the requested language... are eliminated from operation through attrition and/or market forces. One commenter noted...

  14. 78 FR 5800 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-01-28

    ... administrative order assessing a civil penalty against any person who has violated applicable emergency planning... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity... resolve violations of the Clean Water Act (CWA) and the Emergency Planning and Community Right-to-Know...

  15. 37 GHz methanol masers : Horsemen of the Apocalypse for the class II methanol maser phase?

    CERN Document Server

    Ellingsen, S P; Sobolev, A M; Voronkov, M A; Caswell, J L; Lo, N

    2011-01-01

    We report the results of a search for class II methanol masers at 37.7, 38.3 and 38.5 GHz towards a sample of 70 high-mass star formation regions. We primarily searched towards regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesised to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  16. Influence of composite resin consistency and placement technique on proximal contact tightness of Class II restorations.

    NARCIS (Netherlands)

    Loomans, B.A.C.; Opdam, N.J.M.; Roeters, F.J.M.; Bronkhorst, E.M.; Plasschaert, A.J.M.

    2006-01-01

    PURPOSE: To investigate the influence of composite resin consistency and placement technique on proximal contact tightness of Class II composite resin restorations. MATERIALS AND METHODS: A manikin model (KaVo Dental) was used with an artificial first molar in which a standardized MO preparation was

  17. DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis

    DEFF Research Database (Denmark)

    Morling, N; Friis, J; Fugger, L;

    1991-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments a...

  18. Guided tissue regeneration in the treatment of class II furcation defects

    Directory of Open Access Journals (Sweden)

    Tatiana Miranda DELIBERADOR

    2008-12-01

    Full Text Available Introduction: Numerous surgical techniques have been evaluated toattempt the regeneration of furcation defects. Objective and literature review: Among the regenerative techniques, guided tissue regeneration(GTR has been largely used in the treatment of class II furcation defects, the main indication for GTR. Several clinical studies have compared the GTR technique with surgical debridement alone for the treatment of class II furcation defects in mandibular molars. A number of membrane materials have been tested in those studies.Varying results have been observed using non-absorbable expanded polytetrafluoroethylene (e-PTFE membranes. In some studies, the difference between the treatments was not clinically significant. When second generation absorbable membranes were used, the clinicalresults were also variable. However, some clinical studies foundfavorable results using the GTR technique, especially when a polylactic acid membrane was used. Similar modest results were observed when absorbable and non-absorbable membranes were compared clinically in the treatment of class II furcation defects in mandibular molars.Significant differences were not found between the membranes for most of the clinical parameters evaluated.Conclusion: Considering the literature, it can be concluded that the use of GTR for the treatment of mandibular molars with class II furcation defects yielded highly variable and unpredictable results.

  19. A Cephalometric Comparison of Twin Block and Bionator Appliances in Treatment of Class II Malocclusion

    Science.gov (United States)

    Ahmadian-Babaki, Fatemeh; Araghbidi-Kashani, S. Mehdi

    2017-01-01

    Background Class II malocclusion is one of the most common orthodontic problems. In cases of class II malocclusion with mandibular deficiency, functional appliances often are used with the intent of stimulating mandibular growth. Bionator and twin block are two of the more popular functional appliances. The aim of this study was to compare the treatment outcomes of these two appliances using cephalometric radiographs. Material and Methods Cephalometric radiographs of 33 patients who had class II division I malocclusion, before and after treatment were digitalized. The mean changes in twin block and bionator groups were compared using independent t test. Results Twin block and bionator showed no statistically significant differences in cephalometric parameters except for ANB, NA-Pog, Basal and Ar-Go-Me angles. Conclusions There were no statistically significant differences in dentoalveolar and mandibular position between twin block and bionator (p>0.1). Twin block was more efficient in inhibition of forward movement of maxilla (p<0.1). Key words:Functional, Class II malocclusion, Cephalometrics, Twin block, Bionator, Treatment. PMID:28149473

  20. 40 CFR 82.70 - Nonessential Class II products and exceptions.

    Science.gov (United States)

    2010-07-01

    ... limited to household, industrial, automotive and pesticide uses; (2) Except— (i) Medical devices listed in...; (iii) Lubricants, coatings or cleaning fluids used for aircraft maintenance, which contain class II... books, books with coated, dense or paper and tightly bound documents; (vii) Portable fire...

  1. Comparison of Activator-Headgear and Twin Block Treatment Approaches in Class II Division 1 Malocclusion

    Science.gov (United States)

    Mroz Tranesen, Kate; Birkeland, Kari; Katic, Visnja; Pavlic, Andrej; Vandevska-Radunovic, Vaska

    2017-01-01

    The purpose was to compare the treatment effects of functional appliances activator-headgear (AH) and Twin Block (TB) on skeletal, dental, and soft-tissue structures in class II division 1 malocclusion with normal growth changes in untreated subjects. The sample included 50 subjects (56% females) aged 8–13 years with class II division 1 malocclusion treated with either AH (n = 25) or TB (n = 25) appliances. Pre- and posttreatment lateral cephalograms were evaluated and compared to 50 untreated class II division 1 cases matched by age, gender, ANB angle, and skeletal maturity. A paired sample, independent samples tests and discriminant analysis were performed for intra- and intergroup analysis. Treatment with both appliances resulted in significant reduction of skeletal and soft-tissue facial convexity, the overjet, and the prominence of the upper lip in comparison to untreated individuals (p < 0.001). Retroclination of maxillary incisors and proclination of mandibular incisors were seen, the latter being significantly more evident in the TB group (p < 0.05). Increase of effective mandibular length was more pronounced in the TB group. In conclusion, both AH and TB appliances contributed successfully to the correction of class II division 1 malocclusion when compared to the untreated subjects with predominantly dentoalveolar changes. PMID:28203569

  2. [Features of the hormonal status in patients with temporomandibular joint dysfunction and class II malocclusion].

    Science.gov (United States)

    Gus, L A; Arsenina, O I; Komolov, I S

    2015-01-01

    The article presents data on androgen levels in female patients with temporomandibular joint (TMJ) dysfunction of varying degree and class II malocclusion. The study revealed significant correlation between degenerative and inflammatory TMJ changes and androgens level in patients with stigmas of connective tissue dysplasia (p<0.05), probably due to indirect proinflammatory action of androgens as they stimulate inflammatory mediators expression.

  3. 40 CFR 147.250 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... State of California, except those on Indian lands, is the program administered by the California... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class II wells. 147.250 Section 147.250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  4. Comparison of interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns using cone-beam computed tomography

    Science.gov (United States)

    Khumsarn, Nattida; Patanaporn, Virush; Jotikasthira, Dhirawat

    2016-01-01

    Purpose This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Materials and Methods Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Results Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. Conclusion In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns. PMID:27358819

  5. Comparison of interradicular distances and cortical bone thickness in Thai patients with class I and class II skeletal patterns using cone-beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Khumsarn, Nattida [Dental Division of Lamphun Hospital, Lamphun (Thailand); Patanaporn, Virush; Janhom, Apirum; Jotikasthira, Dhirawat [Faculty of Dentistry, Chiang Mai University, Chiang Mai (Thailand)

    2016-06-15

    This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns.

  6. HIV-1 proteins in infected cells determine the presentation of viral peptides by HLA class I and class II molecules and the nature of the cellular and humoral antiviral immune responses--a review.

    Science.gov (United States)

    Becker, Y

    1994-07-01

    The goals of molecular virology and immunology during the second half of the 20th century have been to provide the conceptual approaches and the tools for the development of safe and efficient virus vaccines for the human population. The success of the vaccination approach to prevent virus epidemics was attributed to the ability of inactivated and live virus vaccines to induce a humoral immune response and to produce antiviral neutralizing antibodies in the vaccinees. The successful development of antiviral vaccines and their application to most of the human population led to a marked decrease in virus epidemics around the globe. Despite this remarkable achievement, the developing epidemics of HIV-caused AIDS (accompanied by activation of latent herpesviruses in AIDS patients), epidemics of Dengue fever, and infections with respiratory syncytial virus may indicate that conventional approaches to the development of virus vaccines that induce antiviral humoral responses may not suffice. This may indicate that virus vaccines that induce a cellular immune response, leading to the destruction of virus-infected cells by CD8+ cytotoxic T cells (CTLs), may be needed. Antiviral CD8+ CTLs are induced by viral peptides presented within the peptide binding grooves of HLA class I molecules present on the surface of infected cells. Studies in the last decade provided an insight into the presentation of viral peptides by HLA class I molecules to CD8+ T cells. These studies are here reviewed, together with a review of the molecular events of virus replication, to obtain an overview of how viral peptides associate with the HLA class I molecules. A similar review is provided on the molecular pathway by which viral proteins, used as subunit vaccines or inactivated virus particles, are taken up by endosomes in the endosome pathway and are processed by proteolytic enzymes into peptides that interact with HLA class II molecules during their transport to the plasma membrane of antigen-presenting

  7. Rationale for referring class II patients for early orthodontic treatment As razões para indicação de tratamento precoce em pacientes de classe II

    Directory of Open Access Journals (Sweden)

    José Augusto Mendes Miguel

    2005-09-01

    Full Text Available The tendency of indicating early treatment (before growth spurt when dealing with Angle Class II cases has been noticed, although there is no definite scientific evidence to justify such decision. The aim of this study was to identify the advantages and disadvantages to this approach and which appliances are used for this purpose. For that purpose, a questionnaire containing full records of a Class II patient was sent to two professors of each Orthodontic graduate program in Brazil (n=96, total 192, from which 107 were properly answered. Results demonstrated that the most used appliances were the headgear (80.4%, maxillary splint (50% and Bionator (44.4%. The benefits most often quoted were increase of patient self-esteem (78.5% and reduction in the incidence of incisors trauma (63.6%, while the main disadvantage was saturation of patient compliance (73.8%. Considering early Class II treatment, there is still no unanimity as to treating in one or two stages or in selection of appliances. However, the orthodontists should consider the physical situation of the patient, severity of cases and susceptibility of trauma to the maxillary incisors. It is crucial that updated information is given to parents, in order to justify this approach.A tendência de indicação de tratamento precoce (antes de surto de crescimento para casos de Classe II de Angle tem sido observada, embora não haja evidência científica para embasar tal decisão. O objetivo deste estudo foi identificar as vantagens e desvantagens da indicação e quais aparelhos são usados no tratamento. Foram enviados questionários (n=192 com a documentação completa de um paciente Classe II para dois professores de cada curso de especialização em Ortodontia no Brasil, os quais 107 foram respondidos. Os resultados demonstraram que os aparelhos mais usados foram: Extra-oral (80,4%, Thurow (50,0% e Bionator (44,4%. Foram citados como maiores vantagens: aumento de auto-estima do paciente (78

  8. 56-month clinical performance of Class I and II resin composite restorations

    Directory of Open Access Journals (Sweden)

    Flavia Bittencourt Pazinatto

    2012-06-01

    Full Text Available OBJECTIVE: This study evaluated the 56-month clinical performance of Class I and II resin composite restorations. Filtek P60 was compared with Filtek Z250, which are both indicated for posterior restorations but differ in terms of handling characteristics. The null hypothesis tested was that there is no difference in the clinical performance of the two resin composites in posterior teeth. MATERIAL AND METHODS: Thirty-three patients were treated by the same operator, who prepared 48 Class I and 42 Class II cavities, which were restored with Single Bond/Filtek Z250 or Single Bond/Filtek P60 restorative systems. Restorations were evaluated by two independent examiners at baseline and after 56 months, using the modified USPHS criteria. Data were analyzed statistically using Chi-square and Fisher's Exact tests (a=0.05. RESULTS: After 56 months, 25 patients (31 Class I and 36 Class II were analyzed. A 3% failure rate occurred due to secondary caries and excessive loss of anatomic form for P60. For both restorative systems, there were no significant differences in secondary caries and postoperative sensitivity. However, significant changes were observed with respect to anatomic form, marginal discoloration, and marginal adaptation. Significant decreases in surface texture were observed exclusively for the Z250 restorations. CONCLUSIONS: Both restorative systems can be used for posterior restorations and can be expected to perform well in the oral environment.

  9. Predicting peptides binding to MHC class II molecules using multi-objective evolutionary algorithms

    Directory of Open Access Journals (Sweden)

    Feng Lin

    2007-11-01

    Full Text Available Abstract Background Peptides binding to Major Histocompatibility Complex (MHC class II molecules are crucial for initiation and regulation of immune responses. Predicting peptides that bind to a specific MHC molecule plays an important role in determining potential candidates for vaccines. The binding groove in class II MHC is open at both ends, allowing peptides longer than 9-mer to bind. Finding the consensus motif facilitating the binding of peptides to a MHC class II molecule is difficult because of different lengths of binding peptides and varying location of 9-mer binding core. The level of difficulty increases when the molecule is promiscuous and binds to a large number of low affinity peptides. In this paper, we propose two approaches using multi-objective evolutionary algorithms (MOEA for predicting peptides binding to MHC class II molecules. One uses the information from both binders and non-binders for self-discovery of motifs. The other, in addition, uses information from experimentally determined motifs for guided-discovery of motifs. Results The proposed methods are intended for finding peptides binding to MHC class II I-Ag7 molecule – a promiscuous binder to a large number of low affinity peptides. Cross-validation results across experiments on two motifs derived for I-Ag7 datasets demonstrate better generalization abilities and accuracies of the present method over earlier approaches. Further, the proposed method was validated and compared on two publicly available benchmark datasets: (1 an ensemble of qualitative HLA-DRB1*0401 peptide data obtained from five different sources, and (2 quantitative peptide data obtained for sixteen different alleles comprising of three mouse alleles and thirteen HLA alleles. The proposed method outperformed earlier methods on most datasets, indicating that it is well suited for finding peptides binding to MHC class II molecules. Conclusion We present two MOEA-based algorithms for finding motifs

  10. Treatment of Class II open bite in the mixed dentition with a removable functional appliance and headgear.

    Science.gov (United States)

    Ngan, P; Wilson, S; Florman, M; Wei, S H

    1992-05-01

    Early diagnosis of patients exhibiting open bites that are complicated by skeletal Class II and vertical growth problems can facilitate subsequent treatment. Eight patients with Class II skeletal open bite were treated with the high-pull activator appliance and compared to reasonably matched controls to determine the effects of the appliance. The high-pull activator was found to reduce forward growth of the maxilla and increase mandibular alveolar height, transforming the Class II molar relationship into a Class I molar relationship. The overjet and open bite were decreased, and, in addition, the appliance reduced the amount of forward and downward movement of the maxillary molars, providing vertical control of the maxilla during Class II orthopedic correction. These results demonstrated that open bite complicated by a Class II vertical growth pattern can be treated during the mixed dentition with favorable results by a combination of a removable functional appliance and high-pull headgear.

  11. Class I and Class II restorations of resin composite: an FE analysis of the influence of modulus of elasticity on stresses generated by occlusal loading

    DEFF Research Database (Denmark)

    Asmussen, Erik; Peutzfeldt, Anne

    2008-01-01

    was that the marginal stresses would decrease with increasing modulus of elasticity of the restoration. METHODS: A cylindrical tooth was modelled in enamel and dentin and fitted with a Class I or a Class II restoration of resin composite. In one scenario the restoration was bonded to the tooth, in another......OBJECTIVES: It was the aim of the study to analyze by the FE method stresses generated in tooth and restoration by occlusal loading of Class I and Class II restorations of resin composite. On the basis of available information on the influence of the modulus of elasticity, the research hypothesis...

  12. Class II treatment by extraction of maxillary first molars or Herbst appliance: dentoskeletal and soft tissue effects in comparison

    NARCIS (Netherlands)

    Booij, J.W.; Goeke, J.; Bronkhorst, E.M.; Katsaros, C.; Ruf, S.

    2013-01-01

    AIM: To compare dentoskeletal and soft tissue treatment effects of two alternative Class II division 1 treatment modalities (maxillary first permanent molar extraction versus Herbst appliance). METHODS: One-hundred-fifty-four Class II division 1 patients that had either been treated with extractions

  13. Influence of unilateral maxillary first molar extraction treatment on second and third molar inclination in Class II subdivision patients

    NARCIS (Netherlands)

    Livas, Christos; Pandis, Nikolaos; Booij, Johan Willem; Halazonetis, Demetrios J.; Katsaros, Christos; Ren, Yijin

    2016-01-01

    Objective: To assess the maxillary second molar (M2) and third molar (M3) inclination following orthodontic treatment of Class II subdivision malocclusion with unilateral maxillary first molar (M1) extraction. Materials and Methods: Panoramic radiographs of 21 Class II subdivision adolescents (eight

  14. 40 CFR 144.21 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells.

    Science.gov (United States)

    2010-07-01

    ... recovery and hydrocarbon storage) and III wells. 144.21 Section 144.21 Protection of Environment... hydrocarbon storage) and III wells. (a) An existing Class I, II (except enhanced recovery and hydrocarbon... decision; or (9) For Class II wells (except enhanced recovery and hydrocarbon storage), five years...

  15. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

    DEFF Research Database (Denmark)

    Odum, Niels; Kanner, S B; Ledbetter, J A;

    1993-01-01

    tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...

  16. Survival of self-etch adhesive Class II composite restorations using ART and conventional cavity preparations in primary molars.

    NARCIS (Netherlands)

    Eden, E.; Topaloglu-Ak, A.; Frencken, J.E.F.M.; Hof, M.A. van 't

    2006-01-01

    PURPOSE: To test the null-hypothesis that there was no difference in the survival percentages of Class II composite restorations in primary teeth produced through either ART or conventional approaches after 2 years. METHODS: 157 children with 325 Class II cavitated dentin lesions were included in a

  17. 75 FR 70271 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-17

    ... wound therapy into class II (special controls) under section 513(f)(2) of the Federal Food, Drug, and... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Non-Powered Suction Apparatus Device Intended for...

  18. 76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-04-14

    ... into class II (special controls) under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use;...

  19. Má oclusão Classe II, 2ª Divisão de Angle, com sobremordida acentuada Angle Class II, Division 2, malocclusion with deep overbite

    Directory of Open Access Journals (Sweden)

    Paulo Renato Carvalho Ribeiro

    2010-02-01

    Full Text Available Este relato de caso descreve o tratamento ortodôntico de uma paciente adulta, portadora de uma má oclusão Classe II, 2ª Divisão de Angle, com sobremordida e curva de Spee acentuadas e que apresentava vestibuloversão do dente 12 e algumas recessões gengivais. A paciente foi tratada com exodontia dos primeiros pré-molares superiores e máximo controle de ancoragem. Esse caso foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, representando a categoria 6, ou seja, uma má oclusão com sobremordida acentuada, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.This case report describes the orthodontic treatment of an adult patient, who presented a Angle Class II, Division 2, malocclusion, with overbite, severe curve of Spee, right maxillary lateral incisor proclined and gengival recessions. The patient was treated with extraction of the first premolars and maximum anchorage control. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO representing the category 6, deep overbite malocclusion, as part of the requirements for obtaining the title of Diplomate by BBO.

  20. Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Stanley K.L. [Singapore Immunology Network A-STAR (Singapore); Neo, Soek-Ying, E-mail: neo_soek_ying@sics.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Yap, Yann-Wan [Singapore Immunology Network A-STAR (Singapore); Karuturi, R. Krishna Murthy; Loh, Evelyn S.L. [Genome Institute of Singapore A-STAR (Singapore); Liau, Kui-Hin [Department of General Surgery, Tan Tock Seng Hospital (Singapore); Ren, Ee-Chee, E-mail: ren_ee_chee@immunol.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)

    2009-09-18

    Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2{alpha}) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2{alpha} mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2{alpha} was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2{alpha} can modulate HCC cell growth.

  1. Skeletal and dental changes induced by bionator in early treatment of class II

    Directory of Open Access Journals (Sweden)

    Dirceu Barnabé Raveli

    2016-09-01

    Full Text Available The purpose was to investigate the amount of skeletal and dentoalveolar changes after early treatment of Class II, Division 1 malocclusion with bionator appliance in prepubertal growing patients. Forty Class II patients were divided in two groups. Treated group consisted of 20 subjects treated consecutively with bionator. Mean age at the start of treatment (T0 was 9.1 years, while it was 10.6 years at the end of treatment (T1. Mean treatment time was 17.7 months. Pretreatment and post-treatment cephalometric records of treated group were evaluated and compared with a control group consisted of 20 patients with untreated Class II malocclusion. Intergroup comparisons were performed using Student’s t-tests and chi-square test with Yates’ correction at a significance level of 5 per cent. Bionator appliance was effective in generating differential growth between the jaws. Cephalometric skeletal measurements ANB, WITS, Lafh, Co-A and dental L6-Mp, U1.Pp, IsIi, OB, OJ showed statistically significantly different from the control. Bionator induced more dentoalveolar changes than skeletal during treatment in prepubertal stage.

  2. Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules

    Science.gov (United States)

    Park, Yoon-Kyung; Jung, Sundo; Park, Se-Ho

    2016-01-01

    In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-Aq in a murine CIA model. We found that recombinant I-Aq/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-Aq/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis. [BMB Reports 2016; 49(6): 331-336 PMID:26779996

  3. Sculpting MHC class II-restricted self and non-self peptidome by the class I Ag-processing machinery and its impact on Th-cell responses.

    Science.gov (United States)

    Spencer, Charles T; Dragovic, Srdjan M; Conant, Stephanie B; Gray, Jennifer J; Zheng, Mu; Samir, Parimal; Niu, Xinnan; Moutaftsi, Magdalini; Van Kaer, Luc; Sette, Alessandro; Link, Andrew J; Joyce, Sebastian

    2013-05-01

    It is generally assumed that the MHC class I antigen (Ag)-processing (CAP) machinery - which supplies peptides for presentation by class I molecules - plays no role in class II-restricted presentation of cytoplasmic Ags. In striking contrast to this assumption, we previously reported that proteasome inhibition, TAP deficiency or ERAAP deficiency led to dramatically altered T helper (Th)-cell responses to allograft (HY) and microbial (Listeria monocytogenes) Ags. Herein, we tested whether altered Ag processing and presentation, altered CD4(+) T-cell repertoire, or both underlay the above finding. We found that TAP deficiency and ERAAP deficiency dramatically altered the quality of class II-associated self peptides suggesting that the CAP machinery impacts class II-restricted Ag processing and presentation. Consistent with altered self peptidomes, the CD4(+) T-cell receptor repertoire of mice deficient in the CAP machinery substantially differed from that of WT animals resulting in altered CD4(+) T-cell Ag recognition patterns. These data suggest that TAP and ERAAP sculpt the class II-restricted peptidome, impacting the CD4(+) T-cell repertoire, and ultimately altering Th-cell responses. Together with our previous findings, these data suggest multiple CAP machinery components sequester or degrade MHC class II-restricted epitopes that would otherwise be capable of eliciting functional Th-cell responses.

  4. A Class of Asymmetric Gapped Hamiltonians on Quantum Spin Chains and its Characterization II

    Science.gov (United States)

    Ogata, Yoshiko

    2016-06-01

    We give a characterization of the class of gapped Hamiltonians introduced in Part I (Ogata, A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015). The Hamiltonians in this class are given as MPS (Matrix product state) Hamiltonians. In Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), we list up properties of ground state structures of Hamiltonians in this class. In this Part II, we show the converse. Namely, if a (not necessarily MPS) Hamiltonian H satisfies five of the listed properties, there is a Hamiltonian H' from the class by Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), satisfying the following: The ground state spaces of the two Hamiltonians on the infinite interval coincide. The spectral projections onto the ground state space of H on each finite intervals are approximated by that of H' exponentially well, with respect to the interval size. The latter property has an application to the classification problem with open boundary conditions.

  5. A Class of Asymmetric Gapped Hamiltonians on Quantum Spin Chains and its Characterization II

    Science.gov (United States)

    Ogata, Yoshiko

    2016-12-01

    We give a characterization of the class of gapped Hamiltonians introduced in Part I (Ogata, A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015). The Hamiltonians in this class are given as MPS (Matrix product state) Hamiltonians. In Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), we list up properties of ground state structures of Hamiltonians in this class. In this Part II, we show the converse. Namely, if a (not necessarily MPS) Hamiltonian H satisfies five of the listed properties, there is a Hamiltonian H' from the class by Ogata (A class of asymmetric gapped Hamiltonians on quantum spin chains and its classification I, 2015), satisfying the following: The ground state spaces of the two Hamiltonians on the infinite interval coincide. The spectral projections onto the ground state space of H on each finite intervals are approximated by that of H' exponentially well, with respect to the interval size. The latter property has an application to the classification problem with open boundary conditions.

  6. 454 sequencing reveals extreme complexity of the class II Major Histocompatibility Complex in the collared flycatcher

    Directory of Open Access Journals (Sweden)

    Gustafsson Lars

    2010-12-01

    Full Text Available Abstract Background Because of their functional significance, the Major Histocompatibility Complex (MHC class I and II genes have been the subject of continuous interest in the fields of ecology, evolution and conservation. In some vertebrate groups MHC consists of multiple loci with similar alleles; therefore, the multiple loci must be genotyped simultaneously. In such complex systems, understanding of the evolutionary patterns and their causes has been limited due to challenges posed by genotyping. Results Here we used 454 amplicon sequencing to characterize MHC class IIB exon 2 variation in the collared flycatcher, an important organism in evolutionary and immuno-ecological studies. On the basis of over 152,000 sequencing reads we identified 194 putative alleles in 237 individuals. We found an extreme complexity of the MHC class IIB in the collared flycatchers, with our estimates pointing to the presence of at least nine expressed loci and a large, though difficult to estimate precisely, number of pseudogene loci. Many similar alleles occurred in the pseudogenes indicating either a series of recent duplications or extensive concerted evolution. The expressed alleles showed unambiguous signals of historical selection and the occurrence of apparent interlocus exchange of alleles. Placing the collared flycatcher's MHC sequences in the context of passerine diversity revealed transspecific MHC class II evolution within the Muscicapidae family. Conclusions 454 amplicon sequencing is an effective tool for advancing our understanding of the MHC class II structure and evolutionary patterns in Passeriformes. We found a highly dynamic pattern of evolution of MHC class IIB genes with strong signals of selection and pronounced sequence divergence in expressed genes, in contrast to the apparent sequence homogenization in pseudogenes. We show that next generation sequencing offers a universal, affordable method for the characterization and, in perspective

  7. 40 CFR Figure C-2 to Subpart C of... - Illustration of the Slope and Intercept Limits for Class II and Class III PM2.5 Candidate...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Illustration of the Slope and Intercept Limits for Class II and Class III PM2.5 Candidate Equivalent Methods C Figure C-2 to Subpart C of Part 53... Methods and Reference Methods Pt. 53, Subpt. C, Fig. C-2 Figure C-2 to Subpart C of Part...

  8. CCD surface photometry of radio galaxies: Pt. 1. FR class I and II sources

    Energy Technology Data Exchange (ETDEWEB)

    Owen, F.N.; Laing, R.A.

    1989-05-01

    CCD surface photometry of 47 radio galaxies in the R-band is reported. The goal of the programme is to study the relationship of the properties of the parent galaxies to the radio structure and, in particular, to look for differences between Fanaroff and Riley (FR) class I and II sources. In order to clarify some ambiguous cases in the FR classification, we define Classical Double, Twin Jet and Fat Double sources. We describe our definitions of these three classes and their relation to the FR classification. (author).

  9. Reassessing the role of HLA-DRB3 T-cell responses: evidence for significant expression and complementary antigen presentation.

    Science.gov (United States)

    Faner, Rosa; James, Eddie; Huston, Laurie; Pujol-Borrel, Ricardo; Kwok, William W; Juan, Manel

    2010-01-01

    In humans, several HLA-DRB loci (DRB1/3/4/5) encode diverse beta-chains that pair with alpha-chains to form DR molecules on the surface of APC. While DRB1 and DRB5 have been extensively studied, the role of DRB3/4 products of DR52/DR53 haplotypes has been largely neglected. To clarify the relative expression of DRB3, we quantified DRB3 mRNA levels in comparison with DRB1 mRNA from the same haplotype in both B cells and monocytes, observing quantitatively significant DRB3 synthesis. In CD19+ cells, DRB1*03/11/13 was 3.5-fold more abundant than DRB3, but in CD14+ this difference was only two-fold. Monocytes also had lower overall levels of DR mRNA compared with B cells, which was confirmed by cell surface staining of DRB1 and DRB3. To evaluate the functional role of DRB3, tetramer-guided epitope mapping was used to detect T cells against tetanus toxin and several influenza antigens presented by DRB3*0101/0202 or DRB1*03/11/13. None of the epitopes discovered were shared among any of the DR molecules. Quantitative assessment of DRB3-tetanus toxin specific T cells revealed that they are present at similar frequencies as those observed for DRB1. These results suggest that DRB3 plays a significant role in antigen presentation with different epitopic preferences to DRB1. Therefore, DRB3, like DRB5, serves to extend and complement the peptide repertoire of DRB1 in antigen presentation.

  10. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  11. Characterization and expression pattern ofpouII1,a novel class Ⅱ POU gene in zebrafish

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    POU domain transcription factors that share a conserved DNA-binding domain, POU domain, are important regulators for the development of embryos in various animal species. A novel zebrafish POU domain gene, pouII1has been cloned. The pouII1 cDNA is 2080 kb in length and encodes a putative polypeptide of 596 amino acids. It is placed into class Ⅱ POU family since it shares a high degree of homology with the known members of this family.Northern hybridization identifies a major transcript of approximately 2.1 kb that was present in embryos at the single-cell stage throughout 24 h postfertilizafion. The whole mountin situ hybridization shows thatpouII1 transcripts are present in the single-cell embryos, strongly suggesting that these transcripts are of maternal origin. During early development of the embryos, pouII1 mRNA was ubiquitously distributed in all cells and tissues. The transcripts are gradually limited to brains and become completely undetectable by day 3. To our knowledge, pouII1 is the first class Ⅱ POU gene identified in zebrafish.``

  12. High-density lipoprotein affects antigen presentation by interfering with lipid raft: a promising anti-atherogenic strategy.

    Science.gov (United States)

    Wang, S-H; Yuan, S-G; Peng, D-Q; Zhao, S-P

    2010-05-01

    Atherosclerosis is a chronic inflammatory disease. Immunomodulation of atherosclerosis emerges as a promising approach to prevention and treatment of this widely prevalent disease. The function of high-density lipoprotein (HDL) to promote reverse cholesterol transport may explain the ability of its protection against atherosclerosis. Findings that HDL and apolipoprotein A-I (apoA-I) inhibited the ability of antigen presenting cells (APCs) to stimulate T cells might be attributed to lipid raft, a cholesterol-rich microdomain exhibiting functional properties depending largely upon its lipid composition. Thus, modulating cholesterol in lipid raft may provide a promising anti-atherogenic strategy.

  13. Probiotic metabolites from Bacillus coagulans GanedenBC30TM support maturation of antigen-presenting cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Kathleen F Benson; Kimberlee A Redman; Steve G Carter; David Keller; Sean Farmer; John R Endres; Gitte S Jensen

    2012-01-01

    AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30 (GBC30)bacterial cultures in log phase were used to isolate the secreted metabolite (MET) fraction.A second fraction was made to generate a crude cell-wall-enriched fraction,by centrifugation and lysis,followed by washing.A preparation of MET was subjected to size exclusion centrifugation,generating three fractions:< 3 kDa,3-30 kDa,and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell (PBMC) as a source of antigen-presenting mononuclear phagocytes.The maturation status of mononudear phagocytes was evaluated by staining with monoclonal antibodies towards CD14,CD16,CD80 and CD86 and analyzed by flow cytometry.RESULTS:Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes.The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory ceils,and this property was associated with the high molecular weight metabolite fraction.Changes were also seen for the dendritic cell maturation markers CD80 and CD86.On CD14dim cells,an increase in both CD80 and CD86 expression was seen,in contrast to a selective increase in CD86 expression on CD14bright cells.The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation.The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells.CONCLUSION:The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells,important for immunological decision-making.

  14. Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Løbner, Morten; Cédile, Oriane

    2014-01-01

    BACKGROUND: Tissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells...... but detectable levels of all these cytokines. Transforming growth factor beta expression was similar in all three populations. Although CNS-resident and blood-derived CD11c+ cells showed equivalent ability to induce proliferation of myelin oligodendrocyte glycoprotein-immunised CD4+ T cells, CD11c+ microglia...

  15. Ligation of MHC class I and class II molecules can lead to heterologous desensitization of signal transduction pathways that regulate homotypic adhesion in human lymphocytes.

    Science.gov (United States)

    Wagner, N; Engel, P; Vega, M; Tedder, T F

    1994-06-01

    Engagement of lymphocyte MHC class I and class II Ags activates an array of intracellular signal transduction pathways that up-regulates the activity of cell-surface adhesion receptors, resulting in homotypic cell-cell aggregation. In this study, engagement of MHC class I and class II molecules with specific mAbs was shown to also inhibit lymphocyte homotypic adhesion. Two mAbs reactive with class II Ag, homotypic adhesion blocking mAb (HAB)-2, and HAB-3, and one mAb reactive with class I Ag, HAB-4, were generated that inhibited homotypic adhesion of activated lymphocytes and B and T cell lines at concentrations as low as 0.1 microgram/ml. Binding of these mAbs resulted in heterologous desensitization of other surface signal transduction molecules as homotypic adhesion induced through class I, class II, CD19, CD20, CD39, CD40, Leu-13, and PMA was also inhibited. The spontaneous adhesion exhibited by some cell lines was also abrogated by binding of these mAbs. Abs that either induced, blocked, or had no effect on adhesion bound to distinct epitopes on class I, whereas the anti-class II mAbs recognized either distinct or overlapping epitopes. Thus, engagement of distinct epitopes on MHC molecules can result in homologous or heterologous desensitization of cell-surface signaling molecules. The induction or inhibition of homotypic adhesion through class I molecules did not require the presence of the cytoplasmic domain, as deletion of this portion of the class I molecule had no effect. In contrast, the transmembrane region was essential for signal transduction as the mAbs binding to a chimeric molecule in which the transmembrane and cytoplasmic domains of class I were exchanged with those of the HB15 molecule did not induce or inhibit homotypic adhesion. Although this report is the first demonstration that homotypic adhesion can be influenced in a negative manner through MHC molecules, these findings demonstrate a considerable level of cross-talk between MHC molecules

  16. Characterization of EBV gB indicates properties of both class I and class II viral fusion proteins.

    Science.gov (United States)

    Backovic, Marija; Leser, George P; Lamb, Robert A; Longnecker, Richard; Jardetzky, Theodore S

    2007-11-10

    To gain insight into Epstein-Barr virus (EBV) glycoprotein B (gB), recombinant, secreted variants were generated. The role of putative transmembrane regions, the proteolytic processing and the oligomerization state of the gB variants were investigated. Constructs containing 2 of 3 C-terminal hydrophobic regions were secreted, indicating that these do not act as transmembrane anchors. The efficiency of cleavage of the gB furin site was found to depend on the nature of C-terminus. All of the gB constructs formed rosette structures reminiscent of the postfusion aggregates formed by other viral fusion proteins. However, substitution of putative fusion loop residues, WY(112-113) and WLIY(193-196), with less hydrophobic amino acids from HSV-1 gB, produced trimeric protein and abrogated the ability of the EBV gB ectodomains to form rosettes. These data demonstrate biochemical features of EBV gB that are characteristic of other class I and class II viral fusion proteins, but not of HSV-1 gB.

  17. A Unique Cause of Proteinuria in Pregnancy: Class II Lupus Nephritis with Concomitant Minimal Change Disease

    Science.gov (United States)

    Kunjal, Ryan; Adam-Eldien, Rabie; Makary, Raafat; Jo-Hoy, Francois; Heilig, Charles W.

    2016-01-01

    We report the case of a 22-year-old African American female who presented to another facility for routine follow-up in the 34th week of pregnancy with lower extremity swelling and nephrotic-range proteinuria. Although she was normotensive, it was initially thought that she had preeclampsia. She was monitored carefully and delivery was induced at 37 weeks of gestation. She was transferred to our hospital, where she was diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria. Renal biopsy revealed a surprising finding of minimal change disease (MCD) concomitant with class II lupus nephritis (LN). She was managed with pulses and then tapering doses of steroid therapy with dramatic resolution of the nephrotic syndrome. This case demonstrates not only the rare de novo occurrence of SLE in pregnancy, but the unique finding of MCD coexisting with class II LN. We propose that altered T cell activity may be the link between these seemingly distinct entities.

  18. Efficacy of MTA and CEM Cement with Collagen Membranes for Treatment of Class II Furcation Defects.

    Directory of Open Access Journals (Sweden)

    Habib Ollah Ghanbari

    2014-06-01

    Full Text Available This study aimed to compare the efficacy of MTA and CEM cement in Class II furcation defects in human mandibular molars.Forty furcation defects were treated in 16 patients with chronic periodontitis. The clinical parameters of probing depth (PD, vertical and horizontal clinical attachment levels (VCAL and HCAL, open vertical and horizontal furcation depths (OVFD and OHFD, and gingival margin level (GML were measured at baseline and at 3- and 6-month (re-entry surgery postoperatively. Data were analyzed at a significance level of P<0.05.Use of MTA and CEM caused significant decreases in PD, VCAL, HCAL, OVFD and OHFD at re-entry, with no statistically significant differences between the two treatment options in soft and hard tissue parameters.Both treatment modalities caused significant gains in attachment levels and bone fills, proving efficacy for treatment of Class II furcation involvements.

  19. Camouflage of Severe Skeletal Class II Gummy Smile Patient Treated Nonsurgically with Mini Implants

    Directory of Open Access Journals (Sweden)

    Irfan Qamruddin

    2014-01-01

    Full Text Available Skeletal class II has always been a challenge in orthodontics and often needs assistance of surgical orthodontics in nongrowing patients when it presents with severe discrepancy. Difficulty increases more when vertical dysplasia is also associated with sagittal discrepancy. The advent of mini implants in orthodontics has broadened the spectrum of camouflage treatment. This case report presents a 16-year-old nongrowing girl with severe class II because of retrognathic mandible, and anterior dentoalveolar protrusion sagittally and vertically resulted in severe overjet of 13 mm and excessive display of incisors and gums. Both maxillary central incisors were trimmed by general practitioner few years back to reduce visibility. Treatment involved use of micro implant for retraction and intrusion of anterior maxillary dentoalveolar segment while lower incisors were proclined to obtain normal overjet, and overbite and pleasing soft tissue profile. Smile esthetics was further improved with composite restoration of incisal edges of both central incisors.

  20. In vitro evaluation of the marginal microleakage of class II amalgam restoration associated with dentin adhesive

    Directory of Open Access Journals (Sweden)

    OLIVEIRA Fabiana Sodré de

    1999-01-01

    Full Text Available The marginal microleakage of class II amalgam restorations (Dispersalloy associated with copal varnish (Copalite and with two dentin bonding agents (Scotchbond Multi-uso Plus and Multi Bond Alpha was evaluated in vitro and compared by two methods: scores and linear measurements. Forty-five sound premolars were used, on which two separated class II cavities were prepared on the M and D surfaces. After the restoration, the specimens were thermocycled and stored in a solution of 0.5% basic fuchsin during 24 hours. The analysis allowed to conclude that none of the three restorative systems were able to eliminate the marginal microleakage. Nevertheless, the leakage was significantly smaller on the restorations associated with dentin bonding agents when compared to copal varnish. The linear measurement method was more sensitive than the score criteria.

  1. Target recognition, resistance, immunity and genome mining of class II bacteriocins from Gram-positive bacteria.

    Science.gov (United States)

    Kjos, Morten; Borrero, Juan; Opsata, Mona; Birri, Dagim J; Holo, Helge; Cintas, Luis M; Snipen, Lars; Hernández, Pablo E; Nes, Ingolf F; Diep, Dzung B

    2011-12-01

    Due to their very potent antimicrobial activity against diverse food-spoiling bacteria and pathogens and their favourable biochemical properties, peptide bacteriocins from Gram-positive bacteria have long been considered promising for applications in food preservation or medical treatment. To take advantage of bacteriocins in different applications, it is crucial to have detailed knowledge on the molecular mechanisms by which these peptides recognize and kill target cells, how producer cells protect themselves from their own bacteriocin (self-immunity) and how target cells may develop resistance. In this review we discuss some important recent progress in these areas for the non-lantibiotic (class II) bacteriocins. We also discuss some examples of how the current wealth of genome sequences provides an invaluable source in the search for novel class II bacteriocins.

  2. Evaluation of the position of lower incisors in the mandibular symphysis of individuals with Class II malocclusion and Pattern II profiles

    Directory of Open Access Journals (Sweden)

    Djalma Roque Woitchunas

    2012-06-01

    Full Text Available OBJECTIVES: This study evaluated the position of mandibular incisors in the mandibular symphysis of individuals with Class II malocclusion and Pattern II profiles. METHODS: The sample consisted of 40 Caucasian patients (20 male and 20 female with Class II malocclusion and Pattern II profile from 10 to 18 years of age (mean age of 12.84 years who were selected from the records of the School of Dentistry of Universidade de Passo Fundo, Brazil. The linear cephalometric measurements used in this study were Ricketts' 1- AP, Interlandi's line I and Vigorito's 1-VT; and the angular measurement studied was the mandibular plane angle (IMPA. RESULTS: Mandibular incisors of individuals with Class II malocclusion and Pattern II profile tended to be buccally inclined and protruded.

  3. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Iris J Gonzalez-Leal

    2014-09-01

    Full Text Available Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb and L (Ctsl play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC and macrophages (BMM from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12 expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

  4. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

    Science.gov (United States)

    Gonzalez-Leal, Iris J; Röger, Bianca; Schwarz, Angela; Schirmeister, Tanja; Reinheckel, Thomas; Lutz, Manfred B; Moll, Heidrun

    2014-09-01

    Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb) and L (Ctsl) play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC) and macrophages (BMM) from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT) and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12) expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

  5. Preventing postoperative tooth sensitivity in class I, II and V restorations.

    Science.gov (United States)

    Christensen, Gordon J

    2002-02-01

    Postoperative tooth sensitivity in Class I, II and V resin-based composite restorations continues to be an unpredictable problem in dentistry. In spite of meticulous use of dentin bonding agents, dentists and patients are faced with the sensitivity problem and the frustrating need to remove restorations and occasionally accomplish endodontic therapy on teeth that were not sensitive before the restorations were placed. Practitioners have developed numerous preventive methods to overcome the sensitivity challenge, which I have described in this article.

  6. Unilateral Maxillary First Molar Extraction in Class II Subdivision: An Unconventional Treatment Alternative

    OpenAIRE

    J. W. Booij; Christos Livas

    2016-01-01

    The asymmetrical intra-arch relationship in Class II subdivision malocclusion poses challenges in the treatment planning and mechanotherapy of such cases. This case report demonstrates a treatment technique engaging unilateral extraction of a maxillary first molar and Begg fixed appliances. The outcome stability and the enhancing effect on the eruption of the third molar in the extraction segment were confirmed by a 4-year follow-up examination.

  7. Unilateral Maxillary First Molar Extraction in Class II Subdivision: An Unconventional Treatment Alternative

    Directory of Open Access Journals (Sweden)

    J. W. Booij

    2016-01-01

    Full Text Available The asymmetrical intra-arch relationship in Class II subdivision malocclusion poses challenges in the treatment planning and mechanotherapy of such cases. This case report demonstrates a treatment technique engaging unilateral extraction of a maxillary first molar and Begg fixed appliances. The outcome stability and the enhancing effect on the eruption of the third molar in the extraction segment were confirmed by a 4-year follow-up examination.

  8. Class II, Division 1 Angle malocclusion with severe proclination of maxillary incisors

    Directory of Open Access Journals (Sweden)

    Kátia Montanha

    2016-02-01

    Full Text Available Protrusion of maxillary incisors is a common complaint among patients seeking orthodontic treatment. This report addresses the correction of Class II Angle malocclusion with excessively bucally proclined maxillary incisors, in an adolescent female patient, through the use of extraoral and fixed appliances. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as part of the requirements for obtaining the title of certified by the BBO.

  9. Treatment of a Class II division 1 anterior open bite malocclusion.

    Science.gov (United States)

    Ong, H B

    2001-06-01

    A case report of an 11-year-old Caucasian female who presented with a Class II div I anterior open bite malocclusion. Overjet is 6 mm and the anterior open bite 2 mm. There was a history of digit sucking till she was eight years old. She was successfully treated by non-extraction with pre-adjusted Edgewise appliances and high-pull headgear for a period of 27 months.

  10. Low major histocompatibility complex class II diversity in European and North American moose.

    OpenAIRE

    1995-01-01

    Major histocompatibility complex (MHC) genes encode cell surface proteins whose function is to bind and present intracellularly processed peptides to T lymphocytes of the immune system. Extensive MHC diversity has been documented in many species and is maintained by some form of balancing selection. We report here that both European and North American populations of moose (Alces alces) exhibit very low levels of genetic diversity at an expressed MHC class II DRB locus. The observed polymorphi...

  11. Anteroposterior and vertical changes in skeletal class II patients treated with modified Thurow appliance.

    Science.gov (United States)

    Pithon, Matheus Melo; dos Santos, Rogério Lacerda; Sampaio, Gêisa Aiane de Morais; de Meneses, Izaura Helena Chaves; Coqueiro, Raildo Silva

    2014-01-01

    The aim of this study was to evaluate the post-treatment anteroposterior and vertical alterations in skeletal Class II malocclusion with different maxillary patterns in patients treated with modified Thurow appliance. Forty-five patients (22 girls and 23 boys) with skeletal Class II and angle SN.GoGn ≤ 35 and different maxillary patterns (n = 15), as follows: retrusive (SNA84°) maxilla; mean age 9 years at pre-treatment (T1) and 9 years and 10 months at post-treatment (T2), were treated with modified Thurow cervical traction appliance, with expander screw and extraoral face bow with 10° to 20° fold in relation to the intraoral arch. Force of 500 gf was applied and use for 12 to 14 h/day, with fortnightly adjustments. Analysis of variance ANOVA followed by post-hoc Tukey and Kruskal-Wallis test, followed by Mann-Whitney were used (α = 5%). In changes obtained from stage T1 to T2, no statistically significant differences were found among the groups Protrusive, normal and retrusive maxilla for the variables SNB, SN.GoGn, 1.NA, overjet, overbite and Class II discrepancy (right and left) (p>0.05). Angular measurements SNA and ANB in the protrusive maxilla group were significantly greater than in the normal and retrusive maxilla groups (p0.05). Within the limits of this study, it may be concluded that the modified Thurow cervical traction appliance was efficient for the correction of skeletal Class II irrespective of the maxillary pattern. The mandible had no significant rotation during treatment.

  12. Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model

    Directory of Open Access Journals (Sweden)

    Mittelmann Hans D

    2010-01-01

    Full Text Available Abstract Background The binding of peptide fragments of extracellular peptides to class II MHC is a crucial event in the adaptive immune response. Each MHC allotype generally binds a distinct subset of peptides and the enormous number of possible peptide epitopes prevents their complete experimental characterization. Computational methods can utilize the limited experimental data to predict the binding affinities of peptides to class II MHC. Results We have developed the Regularized Thermodynamic Average, or RTA, method for predicting the affinities of peptides binding to class II MHC. RTA accounts for all possible peptide binding conformations using a thermodynamic average and includes a parameter constraint for regularization to improve accuracy on novel data. RTA was shown to achieve higher accuracy, as measured by AUC, than SMM-align on the same data for all 17 MHC allotypes examined. RTA also gave the highest accuracy on all but three allotypes when compared with results from 9 different prediction methods applied to the same data. In addition, the method correctly predicted the peptide binding register of 17 out of 18 peptide-MHC complexes. Finally, we found that suboptimal peptide binding registers, which are often ignored in other prediction methods, made significant contributions of at least 50% of the total binding energy for approximately 20% of the peptides. Conclusions The RTA method accurately predicts peptide binding affinities to class II MHC and accounts for multiple peptide binding registers while reducing overfitting through regularization. The method has potential applications in vaccine design and in understanding autoimmune disorders. A web server implementing the RTA prediction method is available at http://bordnerlab.org/RTA/.

  13. Detection of autoreactive CD4 T cells using major histocompatibility complex class II dextramers

    OpenAIRE

    Kuszynski Charles; Gangaplara Arunakumar; Upadhyaya Bijaya; Massilamany Chandirasegaran; Reddy Jay

    2011-01-01

    Abstract Background Tetramers are useful tools to enumerate the frequencies of antigen-specific T cells. However, unlike CD8 T cells, CD4 T cells - especially self-reactive cells - are challenging to detect with major histocompatibility complex (MHC) class II tetramers because of low frequencies and low affinities of their T cell receptors to MHC-peptide complexes. Here, we report the use of fluorescent multimers, designated MHC dextramers that contain a large number of peptide-MHC complexes ...

  14. HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations.

    Science.gov (United States)

    Fort, M; de Stefano, G F; Cambon-Thomsen, A; Giraldo-Alvarez, P; Dugoujon, J M; Ohayon, E; Scano, G; Abbal, M

    1998-04-01

    HLA class II alleles were identified in 181 healthy unrelated Ethiopian children of both sexes and in 350 European controls from the South of France. The Ethiopian individuals belonged to the two major ethnic groups of the country: Oromo (N=83) and Amhara (N=98). In both panels, genetic polymorphism of HLA class II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and DQB1 loci. Allelic and phenotypic frequencies were compared with those of European controls and other African populations. Construction of HLA class II three-locus haplotypes was also performed. The study revealed some differences between the two groups. Characteristic features of Central and North African populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11 presented one of the lowest gene frequencies in both Ethiopian ethnic groups in contrast to Europeans and West Africans. Furthermore, this decrease was more marked than those observed using serological techniques in other geographically close East African countries. Oromo and Amhara only showed minor differences in spite of their different origins and histories. One significant difference consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West African people. Some new or rare haplotypes were also observed in the Oromo group. Our results underline the distinctive features of the Ethiopian populations among the few HLA genotyping data available for East African groups and emphasise the major interest of such investigations in this region of Africa.

  15. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series.

    Science.gov (United States)

    Verma, Pushpendra Kumar; Srivastava, Ruchi; Gupta, K K; Chaturvedi, T P

    2013-09-01

    Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR), root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  16. Cephalometric changes in Class II division 1 patients treated with two maxillary premolars extraction

    Directory of Open Access Journals (Sweden)

    Marisana Piano Seben

    2013-08-01

    Full Text Available OBJECTIVE: The purpose of this study was to evaluate the cephalometric alterations in patients with Angle Class II division 1 malocclusion, orthodontically treated with extraction of two maxillary premolars. METHODS: The sample comprised 68 initial and final lateral cephalograms of 34 patients of both gender (mean initial age of 14.03 years and mean final age of 17.25 years, treated with full fixed appliances and extraction of the first maxillary premolars. In order to evaluate the alterations due the treatment between initial and final phases, the dependent t test was applied to the studied cephalometric variables. RESULTS: The dentoskeletal alterations due to extraction of two maxillary premolars in the Class II division 1 malocclusion were: maxillary retrusion, improvement of the maxillomandibular relation, increase of lower anterior face height, retrusion of the maxillary incisors, buccal inclination, protrusion and extrusion of the mandibular incisors, besides the reduction of overjet and overbite. The tissue alterations showed decrease of the facial convexity and retrusion of the upper lip. CONCLUSIONS: The extraction of two maxillary premolars in Class II division 1 malocclusion promotes dentoskeletal and tissue alterations that contribute to an improvement of the relation between the bone bases and the soft tissue profile.

  17. Class II malocclusion treatment using high-pull headgear with a splint: a systematic review

    Directory of Open Access Journals (Sweden)

    Helder B. Jacob

    2013-04-01

    Full Text Available OBJECTIVE: To systematically review the scientific evidence pertaining to the effectiveness of high-pull headgear in growing Class II subjects. METHODS: A literature survey was performed by electronic database search. The survey covered the period from January 1966 to December 2008 and used Medical Subject Headings (MeSH. Articles were initially selected based on their titles and abstracts; the full articles were then retrieved. The inclusion criteria included growing subjects between 8 to 15 years of age, Class II malocclusion treatment with high-pull headgear, and a control group with Class II malocclusion. References from selected articles were hand-searched for additional publications. Selected studies were evaluated methodologically. RESULTS: Four articles were selected; none were randomized controlled trials. All of the articles clearly formulated their objectives and used appropriate measures. The studies showed that high-pull headgear treatment improves skeletal and dental relationship, distal displacement of the maxilla, vertical eruption control and upper molars distalization. One of the studies showed a slight clockwise rotation of the palatal plane; the others showed no significant treatment effect. The mandible was not affected by the treatment. CONCLUSION: While there is still a lack of strong evidence demonstrating the effects of high-pull headgear with a splint, other studies indicate that the AP relations improve due to distalization of the maxilla and upper molars, with little or no treatment effects in the mandible. Greater attention to the design should be given to improve the quality of such trials.

  18. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2013-01-01

    Full Text Available Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR, root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  19. Treatment timing of MARA and fixed appliance therapy of Class II malocclusion.

    Science.gov (United States)

    Ghislanzoni, Luis Tomas Huanca; Baccetti, Tiziano; Toll, Douglas; Defraia, Efisio; McNamara, James A; Franchi, Lorenzo

    2013-06-01

    The objective of this study is to evaluate the effect of timing on Mandibular Anterior Repositioning Appliance (MARA) and fixed appliance treatment of Class II malocclusion in a prospective clinical trial. The treated sample consisted of 51 consecutively treated patients at prepubertal (n = 21), pubertal (n = 15), and postpubertal (n = 15) stages of development. Control groups for the three treated groups were generated from growth data of untreated Class II subjects. Lateral cephalograms were digitized and superimposed via cephalometric software at T1 (pre-treatment) and T2 (after comprehensive treatment). The T1-T2 changes in the treated groups were compared to those in their corresponding control groups with Mann-Whitney tests with Bonferroni correction. Mandibular elongation was greater at the pubertal stage (Co-Gn +2.6 mm, with respect to controls). Headgear effect on the maxilla was greater in the pre-peak sample (Co-A -1.9 mm, with respect to controls). Dentoalveolar compensations (proclination of lower incisors, extrusion and mesialization of lower molars, and reduction in the overbite) were significant in the pre-peak and post-peak groups. Optimal timing for Class II treatment with MARA appliance is at the pubertal growth spurt, with enhanced mandibular skeletal changes and minimal dentoalveolar compensations.

  20. Metal-ion dependent catalytic properties of Sulfolobus solfataricus class II α-mannosidase

    DEFF Research Database (Denmark)

    Nielsen, Jonas Willum; Poulsen, Nina Rødtness; Johnsson, Anna Margit Susanne;

    2012-01-01

    The active site for the family GH38 class II α-mannosidase is constituted in part by a divalent metal ion, mostly Zn(2+), as revealed in the crystal structures of enzymes from both animal and bacterial sources. The metal ion coordinates to the bound substrate and side chains of conserved amino acid...... residues. Recently, evidence has accumulated that class II α-mannosidase is active in complex with a range of divalent metal ions. In the present work, with employment of the class II α-mannosidase, ManA, from the hyperthermophilic archaeon Sulfolobus solfataricus, we explored the influence of the divalent...... metal ion on the associated steady-state kinetic parameters, K(M) and k(cat), for various substrates. With p-nitrophenyl-α-d-mannoside as a substrate, the enzyme showed activity in the presence of Co(2+), Cd(2+), Mn(2+), and Zn(2+), whereas Ni(2+) and Cu(2+) were inhibitory and nonactivating. Co(2...

  1. Variation in Class II malocclusion: comparison of Mexican mestizos and American whites.

    Science.gov (United States)

    Phelan, Tom; Buschang, Peter H; Behrents, Rolf G; Wintergerst, Ana M; Ceen, Richard F; Hernandez, Angeles

    2004-04-01

    This study compared the skeletal and dental characteristics of Class II Division 1 white Americans and Mexicans. It was designed specifically to the evaluate ethnic, age, and sex differences of 101 whites and 107 Mexican mestizos, with approximately equal numbers in each subgroup. Three-way analyses of variance were used to simultaneously evaluate the effects of age, sex, ethnicity, and their interactions. Although Mexicans and whites in the United States had similar maxillomandibular relationships, Mexicans showed greater protrusion of the jaws and teeth. Mexican subjects with Class II malocclusions also showed less divergence of the cranial base (SN-FH angle) and greater vertical tendencies (MPA, Y-axis, and palatal plane angle) than their white counterparts. In comparison with children (mean age 9.0 years), young adults (mean age 20.1 years) had significantly larger craniofacial dimensions, jaws that were positioned more forward, and teeth that were more protruded. Sex differences pertained only to size (men were larger) and maxillary incisor angulation (men were more protrusive). The findings pertaining to the ethnic differences have important clinical implications regarding treatment decisions for Mexican and white patients. In addition, this study provides a foundation for future studies pertaining to Class II malocclusion in Mexicans.

  2. Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells.

    Science.gov (United States)

    Herouet, C; Cottin, M; LeClaire, J; Enk, A; Rousset, F

    2000-01-01

    Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.

  3. Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

    Directory of Open Access Journals (Sweden)

    Ian A Cockburn

    2010-05-01

    Full Text Available Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.

  4. Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells.

    Science.gov (United States)

    Klasen, I S; Melief, M J; Swaak, T J; Severijnen, A J; Hazenberg, M P

    1993-01-01

    The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases. PMID:8447692

  5. Luciferase mRNA Transfection of Antigen Presenting Cells Permits Sensitive Nonradioactive Measurement of Cellular and Humoral Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Tana A. Omokoko

    2016-01-01

    Full Text Available Immunotherapy is rapidly evolving as an effective treatment option for many cancers. With the emerging fields of cancer vaccines and adoptive cell transfer therapies, there is an increasing demand for high-throughput in vitro cytotoxicity assays that efficiently analyze immune effector functions. The gold standard 51Cr-release assay is very accurate but has the major disadvantage of being radioactive. We reveal the development of a versatile and nonradioactive firefly luciferase in vitro transcribed (IVT RNA-based assay. Demonstrating high efficiency, consistency, and excellent target cell viability, our optimized luciferase IVT RNA is used to transfect dividing and nondividing primary antigen presenting cells. Together with the long-lasting expression and minimal background, the direct measurement of intracellular luciferase activity of living cells allows for the monitoring of killing kinetics and displays paramount sensitivity. The ability to cotransfect the IVT RNA of the luciferase reporter and the antigen of interest into the antigen presenting cells and its simple read-out procedure render the assay high-throughput in nature. Results generated were comparable to the 51Cr release and further confirmed the assay’s ability to measure antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The assay’s combined simplicity, practicality, and efficiency tailor it for the analysis of antigen-specific cellular and humoral effector functions during the development of novel immunotherapies.

  6. Messenger RNA sequence rather than protein sequence determines the level of self-synthesis and antigen presentation of the EBV-encoded antigen, EBNA1.

    Directory of Open Access Journals (Sweden)

    Judy T Tellam

    2012-12-01

    Full Text Available Unique purine-rich mRNA sequences embedded in the coding sequences of a distinct group of gammaherpesvirus maintenance proteins underlie the ability of the latently infected cell to minimize immune recognition. The Epstein-Barr virus nuclear antigen, EBNA1, a well characterized lymphocryptovirus maintenance protein has been shown to inhibit in cis antigen presentation, due in part to a large internal repeat domain encoding glycine and alanine residues (GAr encoded by a purine-rich mRNA sequence. Recent studies have suggested that it is the purine-rich mRNA sequence of this repeat region rather than the encoded GAr polypeptide that directly inhibits EBNA1 self-synthesis and contributes to immune evasion. To test this hypothesis, we generated a series of EBNA1 internal repeat frameshift constructs and assessed their effects on cis-translation and endogenous antigen presentation. Diverse peptide sequences resulting from alternative repeat reading frames did not alleviate the translational inhibition characteristic of EBNA1 self-synthesis or the ensuing reduced surface presentation of EBNA1-specific peptide-MHC class I complexes. Human cells expressing the EBNA1 frameshift variants were also poorly recognized by antigen-specific T-cells. Furthermore, a comparative analysis of the mRNA sequences of the corresponding repeat regions of different viral maintenance homologues highlights the high degree of identity between the nucleotide sequences despite very little homology in the encoded amino acid sequences. Based on these combined observations, we propose that the cis-translational inhibitory effect of the EBNA1 internal repeat sequence operates mechanistically at the nucleotide level, potentially through RNA secondary structural elements, and is unlikely to be mediated through the GAr polypeptide. The demonstration that the EBNA1 repeat mRNA sequence and not the encoded protein sequence underlies immune evasion in this class of virus suggests a

  7. Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis

    NARCIS (Netherlands)

    M.M. van Luijn (Marvin M.); K.L. Kreft (Karim); M.L. Jongsma (Marlieke L.); S.W. Mes (Steven); A.F. Wierenga-Wolf (Annet); M. van Meurs (Marjan); M.J. Melief (Marie-José); Rv. der Kant (Rik van); L. Janssen (Lennert); H. Janssen (Hans); R. Tan (Rusung); J.J. Priatel (John J.); J. Neefjes (Jacques); J.D. Laman (Jon); R.Q. Hintzen (Rogier)

    2015-01-01

    textabstractC-type lectins are key players in immune regulation by driving distinct functions of antigen-presenting cells. The C-type lectin CLEC16A gene is located at 16p13, a susceptibility locus for several autoimmune diseases, including multiple sclerosis. However, the function of this gene and

  8. Type-II Dirac fermions in the PtSe2 class of transition metal dichalcogenides

    Science.gov (United States)

    Huang, Huaqing; Zhou, Shuyun; Duan, Wenhui

    2016-09-01

    Recently, a new "type-II" Weyl fermion, which exhibits exotic phenomena, such as an angle-dependent chiral anomaly, was discovered in a new phase of matter where electron and hole pockets contact at isolated Weyl points [Nature (London) 527, 495 (2015), 10.1038/nature15768]. This raises an interesting question about whether its counterpart, i.e., a type-II Dirac fermion, exists in real materials. Here, we predict the existence of symmetry-protected type-II Dirac fermions in a class of transition metal dichalcogenide materials. Our first-principles calculations on PtSe2 reveal its bulk type-II Dirac fermions which are characterized by strongly tilted Dirac cones, novel surface states, and exotic doping-driven Lifshitz transition. Our results show that the existence of type-II Dirac fermions in PtSe2-type materials is closely related to its structural P 3 ¯m 1 symmetry, which provides useful guidance for the experimental realization of type-II Dirac fermions and intriguing physical properties distinct from those of the standard Dirac fermions known before.

  9. Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.

    Science.gov (United States)

    Bataille, Arnaud; Cashins, Scott D; Grogan, Laura; Skerratt, Lee F; Hunter, David; McFadden, Michael; Scheele, Benjamin; Brannelly, Laura A; Macris, Amy; Harlow, Peter S; Bell, Sara; Berger, Lee; Waldman, Bruce

    2015-04-22

    The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) can cause precipitous population declines in its amphibian hosts. Responses of individuals to infection vary greatly with the capacity of their immune system to respond to the pathogen. We used a combination of comparative and experimental approaches to identify major histocompatibility complex class II (MHC-II) alleles encoding molecules that foster the survival of Bd-infected amphibians. We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove. Moreover, strong signals of selection acting on these specific sites were evident among all species co-existing with the pathogen. In the laboratory, we experimentally inoculated Australian tree frogs with Bd to test how each binding pocket conformation influences disease resistance. Only the conformation of MHC-II pocket 9 of surviving subjects matched those of Bd-resistant species. This MHC-II conformation thus may determine amphibian resistance to Bd, although other MHC-II binding pockets also may contribute to resistance. Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd. The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.

  10. A extração de segundos molares superiores para o tratamento da Classe II Extraction of upper second molars for treatment of Angle Class II malocclusion

    Directory of Open Access Journals (Sweden)

    Maurício Barbieri Mezomo

    2010-06-01

    Full Text Available Este trabalho tem por objetivo apresentar uma abordagem alternativa para o tratamento ortodôntico das más oclusões de Classe II. Através de uma revisão da literatura, verificou-se que a extração de segundos molares superiores demonstrou ser uma alternativa viável para o tratamento desse tipo de má oclusão. Essa opção terapêutica possibilita maior rapidez na distalização dos primeiros molares com menor necessidade de cooperação por parte do paciente. Porém, a análise do grau de formação, posição intraóssea e morfologia do terceiro molar deve ser cuidadosamente realizada para proporcionar o correto posicionamento do mesmo no lugar do segundo molar extraído. Dois casos clínicos apresentarão a sequência do diagnóstico e tratamento com essa mecânica, exibindo resultados adequados dos pontos de vista funcional e estético.The purpose of this article is to present an alternative approach to the orthodontic treatment of Angle Class II malocclusion. According to a literature review it was observed that the extraction of upper second molars has proven to be a viable alternative for the treatment of this type of malocclusion. This therapeutic option enables faster first molar retraction and requires less patient compliance. However, the level of development, intraosseous position and morphology of the third molar should be carefully evaluated to ensure its correct positioning in place of the extracted second molar. Two clinical case reports will demonstrate that the sequence of diagnosis and treatment used with this mechanics yields satisfactory functional and aesthetic results.

  11. pRB is required for interferon-gamma-induction of the MHC class II abeta gene.

    Science.gov (United States)

    Zhu, X; Pattenden, S; Bremner, R

    1999-09-02

    pRB is required for IFN-gamma-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRB-dependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB+/+ mouse embryonic fibroblasts (MEFs), but deficient in RB-/- MEFs. Inducibility is restored in RB-/- MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was specifically required for induction of the Abeta, but not Aalpha or other MHC cII genes including Ebeta, Ii and H2-Malpha. Finally, IFN-gamma-induction of class II transactivator (CIITA), was pRB-independent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

  12. Complete genome sequence of Lactobacillus paraplantarum L-ZS9, a probiotic starter producing class II bacteriocins.

    Science.gov (United States)

    Liu, Lei; Li, Pinglan

    2016-03-20

    Lactobacillus paraplantarum L-ZS9 is a probiotic starter isolated from fermented sausage and it is a great producer of class II bacteriocins. To the best of our knowledge, this is the first complete sequenced genome of L. paraplantarum deposited in GenBank database. The size of the complete genome of L. paraplantarum L-ZS9 is 3,139,729 bp. The genomic sequence revealed that this strain includes 19 genes involved in class II bacteriocins production and regulation. The information fill the gaps of the L. paraplantarum genome information and contribute to the improvement of class II bacteriocins research.

  13. Treatment of Class II, Division 2 in the late growth period.

    Science.gov (United States)

    Eberhard, H; Hirschfelder, U

    1998-01-01

    The "Deckbiss" with skeletal Class II jaw relationship sometimes presents a considerable therapeutic problem, particularly in the late growth period (DP3U), as regards the coordination of dental and skeletal treatment objectives. An effective treatment approach was demonstrated: a modified Herbst appliance used simultaneously with fixed appliances in the maxilla. The sample comprised 12 male (14.0 +/- 0.9 years old) and 10 female (12.3 +/- 0.4 years old) patients. Correction of the distal occlusion was achieved in all patients by means of the Herbst appliance, which was removed after an average time period of 6.4 +/- 0.2 months. In the mandible the multibracket appliances were then immediately inserted, and Class II elastics were used for retention. Maximum anchorage was required in the maxilla as well as in the mandible. Complete diagnostic records were made at the beginning of the treatment as well as 6 and 12 months later, in order to document skeletal and dental changes. A dental and skeletal Class I relationship was achieved in all cases. A significant improvement was recorded in the vertical jaw base relationship; this was still stable after a period of 12 months. In the dental area in particular, a so-called high-pull headgear effect (intrusion and distalization 16, 26) and intrusion of teeth 34, 44 were registered. Only a minor protrusion of the mandibular incisors was observed. Reinforcement of the bands reduced the failure rate significantly. The Herbst appliance does not represent a standard treatment for Class II. Its indication range is limited.

  14. Variations in cyclic mandibular movements during treatment of Class II malocclusions with removable functional appliances.

    Science.gov (United States)

    Thieme, Kirsten M; Nägerl, Hans; Hahn, Wolfram; Ihlow, Dankmar; Kubein-Meesenburg, Dietmar

    2011-12-01

    The aim of the study was to establish whether juveniles with a Class II malocclusion change the neuromuscular control of mandibular movements during the course of orthodontic treatment with removable functional appliances (RFAs). Neuromuscular control can be indirectly evaluated by recording cyclic planar mandibular movements which were freely carried out by the patients (28 girls, 14 boys, aged 11.1 ± 1.1 years at the start of treatment) and measured with an ultrasonic device before, during, and after Class II functional appliance therapy, with either an activator or a bite jumping plate. The cyclic movements represented simultaneous rotations of the mandible around a maxillary and mandibular fixed axis (MFHA) and could be characterized by μ(α)-diagrams (μ = swing angle of MFHA, α = mouth opening angle) and path length (L) of the MFHA. The μ(α)-diagrams clearly divided into four parts: movement representing protrusion, mouth opening, and two parts of backward closing as known from Posselt diagrams. Parameters from the Posselt and μ(α)-diagrams were checked by one-factor analysis of variance on a 5 per cent significance level for group dependency. For one-third of the patients investigated, no significant changes were seen in any parameter pre- or post-therapy. However, patients showing an initially large mouth opening capacity or a very short condylar path changed their neuromuscular control to that of Class I subjects. Analysis of μ(α)-diagrams provides the possibility of assessing changes in the neuromuscular control of the mandible during Class II treatment.

  15. The properties of the single chicken MHC classical class II alpha chain ( B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

    DEFF Research Database (Denmark)

    Salomonsen, Jan; Marston, Denise; Avila, David;

    2003-01-01

    for the cloning and sequencing of the cDNA. We found only one class II alpha chain transcript, which bears the major features of a classical class II alpha sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most......In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) alpha chain from outbred chickens as the basis...... significantly in the peptide-binding alpha(1) domain. The cDNA and genomic DNA sequences from chickens of diverse origins show few alleles, which differ in only four nucleotides and one amino acid. In contrast, significant restriction fragment length polymorphism is detected by Southern blot analysis of genomic...

  16. Semi-longitudinal Study of the Mcnamara Cephalometric Triangle in Class II and Class III Subjects Grouped by Cervical Vertebrae Maturation Stage.

    Science.gov (United States)

    Arriola-Guillén, Luis E; Fitzcarrald, Fernando D; Flores-Mir, Carlos

    2015-12-01

    The aim was to compare the McNamara cephalometric triangle values in untreated normodivergent Class II and Class III malocclusion subjects of Latin American origin grouped by cervical vertebrae maturation stage to an untreated Class I malocclusion normodivergent control group. The study was conducted on a sample of 610 pretreatment lateral cephalograms (250 male, 360 female), examined and grouped according to their anteroposterior skeletal relationship (Class I, II or III), cervical vertebrae maturation stage (Pre Pubertal Peak P1 = CS1 and CS2, Pubertal Peak P2= CS3 and CS4, and Post Pubertal Peak P3 = CS5 and CS6) and sex. Co-A, Co-Gn and ENA-Me were measured in each lateral cephalogram. ANOVA and Tukey HSD post-hoc tests were performed to determine differences between the groups. The results showed that in males, the greatest maxillary and mandibular dimensional increases occurred during the P3 stage (CS5 to CS6), while in females, they occurred in the P2 stage (CS3 to CS4). The Co-A and Co-Gn showed significant differences between the malocclusion classes (pClass II subjects and the mandibular lengths in Class III subjects were already higher at the beginning of the period evaluated (P1). A worsening trend for the Class II and III malocclusions was identified during the period evaluated. Finally, changes in the McNamara cephalometric triangle values were markedly different in the three normodivergent skeletal malocclusion classes. In these Latin American subjects the pubertal growth spurt occurred at different times with respect to the Caucasian and Asian norms.

  17. Self-esteem in adolescents with Angle Class I, II and III malocclusion in a Peruvian sample

    Directory of Open Access Journals (Sweden)

    Karla Florián-Vargas

    2016-04-01

    Full Text Available ABSTRACT Objective: To compare self-esteem scores in 12 to 16-year-old adolescents with different Angle malocclusion types in a Peruvian sample. Material and Methods: A cross-sectional study was conducted in a sample of 276 adolescents (159, 52 and 65 with Angle Class I, II and III malocclusions, respectively from Trujillo, Peru. Participants were asked to complete the Rosenberg Self-Esteem Scale (RSES and were also clinically examined, so as to have Angle malocclusion classification determined. Analysis of covariance (ANCOVA was used to compare RSES scores among adolescents with Class I, II and III malocclusions, with participants' demographic factors being controlled. Results: Mean RSES scores for adolescents with Class I, II and III malocclusions were 20.47 ± 3.96, 21.96 ± 3.27 and 21.26 ± 4.81, respectively. The ANCOVA test showed that adolescents with Class II malocclusion had a significantly higher RSES score than those with Class I malocclusion, but there were no differences between other malocclusion groups. Supplemental analysis suggested that only those with Class II, Division 2 malocclusion might have greater self-esteem when compared to adolescents with Class I malocclusion. Conclusion: This study shows that, in general, self-esteem did not vary according to adolescents' malocclusion in the sample studied. Surprisingly, only adolescents with Class II malocclusion, particularly Class II, Division 2, reported better self-esteem than those with Class I malocclusion. A more detailed analysis assessing the impact of anterior occlusal features should be conducted.

  18. Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates

    Directory of Open Access Journals (Sweden)

    Gimeno Mariona

    2011-01-01

    Full Text Available Abstract The present study examined the immunological response of antigen presenting cells (APC to genotype-I isolates of porcine reproductive and respiratory syndrome virus (PRRSV infection by analysing the cytokine profile induced and evaluating the changes taking place upon infection on immunologically relevant cell markers (MHCI, MHCII, CD80/86, CD14, CD16, CD163, CD172a, SWC9. Several types of APC were infected with 39 PRRSV isolates. The results show that different isolates were able to induce different patterns of IL-10 and TNF-α. The four possible phenotypes based on the ability to induce IL-10 and/or TNF-α were observed, although different cell types seemed to have different capabilities. In addition, isolates inducing different cytokine-release profiles on APC could induce different expression of cell markers.

  19. Structural determinants for ligand capture by a class II preQ1 riboswitch.

    Science.gov (United States)

    Kang, Mijeong; Eichhorn, Catherine D; Feigon, Juli

    2014-02-11

    Prequeuosine (preQ1) riboswitches are RNA regulatory elements located in the 5' UTR of genes involved in the biosynthesis and transport of preQ1, a precursor of the modified base queuosine universally found in four tRNAs. The preQ1 class II (preQ1-II) riboswitch regulates preQ1 biosynthesis at the translational level. We present the solution NMR structure and conformational dynamics of the 59 nucleotide Streptococcus pneumoniae preQ1-II riboswitch bound to preQ1. Unlike in the preQ1 class I (preQ1-I) riboswitch, divalent cations are required for high-affinity binding. The solution structure is an unusual H-type pseudoknot featuring a P4 hairpin embedded in loop 3, which forms a three-way junction with the other two stems. (13)C relaxation and residual dipolar coupling experiments revealed interhelical flexibility of P4. We found that the P4 helix and flanking adenine residues play crucial and unexpected roles in controlling pseudoknot formation and, in turn, sequestering the Shine-Dalgarno sequence. Aided by divalent cations, P4 is poised to act as a "screw cap" on preQ1 recognition to block ligand exit and stabilize the binding pocket. Comparison of preQ1-I and preQ1-II riboswitch structures reveals that whereas both form H-type pseudoknots and recognize preQ1 using one A, C, or U nucleotide from each of three loops, these nucleotides interact with preQ1 differently, with preQ1 inserting into different grooves. Our studies show that the preQ1-II riboswitch uses an unusual mechanism to harness exquisite control over queuosine metabolism.

  20. The Dimanganese(II) Site of Bacillus subtilis Class Ib Ribonucleotide Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Boal, Amie K.; Cotruvo, Jr., Joseph A.; Stubbe, JoAnne; Rosenzweig, Amy C. (MIT); (NWU)

    2014-10-02

    Class Ib ribonucleotide reductases (RNRs) use a dimanganese-tyrosyl radical cofactor, Mn{sub 2}{sup III}-Y{sm_bullet}, in their homodimeric NrdF ({beta}2) subunit to initiate reduction of ribonucleotides to deoxyribonucleotides. The structure of the Mn{sub 2}{sup II} form of NrdF is an important component in understanding O{sub 2}-mediated formation of the active metallocofactor, a subject of much interest because a unique flavodoxin, NrdI, is required for cofactor assembly. Biochemical studies and sequence alignments suggest that NrdF and NrdI proteins diverge into three phylogenetically distinct groups. The only crystal structure to date of a NrdF with a fully ordered and occupied dimanganese site is that of Escherichia coli Mn{sub 2}{sup II}-NrdF, prototypical of the enzymes from actinobacteria and proteobacteria. Here we report the 1.9 {angstrom} resolution crystal structure of Bacillus subtilis Mn{sub 2}{sup II}-NrdF, representative of the enzymes from a second group, from Bacillus and Staphylococcus. The structures of the metal clusters in the {beta}2 dimer are distinct from those observed in E. coli Mn{sub 2}{sup II}-NrdF. These differences illustrate the key role that solvent molecules and protein residues in the second coordination sphere of the Mn{sub 2}{sup II} cluster play in determining conformations of carboxylate residues at the metal sites and demonstrate that diverse coordination geometries are capable of serving as starting points for Mn{sub 2}{sup III}-Y{sm_bullet} cofactor assembly in class Ib RNRs.

  1. Antigen-presenting cells represent targets for R5 HIV-1 infection in the first trimester pregnancy uterine mucosa.

    Directory of Open Access Journals (Sweden)

    Romain Marlin

    Full Text Available BACKGROUND: During the first trimester of pregnancy, HIV-1 mother-to-child transmission is relatively rare despite the permissivity of placental cells to cell-to-cell HIV-1 infection. The placenta interacts directly with maternal uterine cells (decidual cells but the physiological role of the decidua in the control of HIV-1 transmission and whether decidua could be a source of infected cells is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To answer to this question, decidual mononuclear cells were exposed to HIV-1 in vitro. Decidual cells were shown to be more susceptible to infection by an R5 HIV-1, as compared to an X4 HIV-1. Infected cells were identified by flow cytometry analysis. The results showed that CD14(+ cells were the main targets of HIV-1 infection in the decidua. These infected CD14(+ cells expressed DC-SIGN, CD11b, CD11c, the Fc gamma receptor CD16, CD32 and CD64, classical MHC class-I and class-II and maturation and activation molecules CD83, CD80 and CD86. The permissivity of decidual tissue was also evaluated by histoculture. Decidual tissue was not infected by X4 HIV-1 but was permissive to R5 HIV-1. Different profiles of infection were observed depending on tissue localization. CONCLUSIONS/SIGNIFICANCE: The presence of HIV-1 target cells in the decidua in vitro and the low rate of in utero mother-to-child transmission during the first trimester of pregnancy suggest that a natural control occurs in vivo limiting cell-to-cell infection of the placenta and consequently infection of the fetus.

  2. Energy-optimised pharmacophore approach to identify potential hotspots during inhibition of Class II HDAC isoforms.

    Science.gov (United States)

    Ganai, Shabir Ahmad; Shanmugam, Karthi; Mahadevan, Vijayalakshmi

    2015-01-01

    Histone deacetylases (HDACs) are conjugated enzymes that modulate chromatin architecture by deacetylating lysine residues on the histone tails leading to transcriptional repression. Pharmacological interventions of these enzymes with small molecule inhibitors called Histone deacetylase inhibitors (HDACi) have shown enhanced acetylation of the genome and are hence emerging as potential targets at the clinic. Type-specific inhibition of Class II HDACs has shown enhanced therapeutic benefits against developmental and neurodegenerative disorders. However, the structural identity of class-specific isoforms limits the potential of their inhibitors in precise targeting of their enzymes. Diverse strategies have been implemented to recognise the features in HDAC enzymes which may help in identifying isoform specificity factors. This work attempts a computational approach that combines in silico docking and energy-optimised pharmacophore (E-pharmacophore) mapping of 18 known HDAC inhibitors and has identified structural variations that regulate their interactions against the six Class II HDAC enzymes considered for the study. This combined approach establishes that inhibitors possessing higher number of aromatic rings in different structural regions might function as potent inhibitors, while inhibitors with scarce ring structures might point to compromised potency. This would aid the rationale for chemical optimisation and design of isoform selective HDAC inhibitors with enhanced affinity and therapeutic efficiency.

  3. Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules

    Energy Technology Data Exchange (ETDEWEB)

    Scholl, P.; Diez, A.; Mourad, W.; Parsonnet, J.; Geha, R.S.; Chatila, T. (Harvard Medical School, Boston, MA (USA))

    1989-06-01

    Toxic shock syndrome toxin 1 (TSST-1) is a 22-kDa exotoxin produced by strains of Staphylococcus aureus and implicated in the pathogenesis of toxic shock syndrome. In common with other staphylococcal exotoxins, TSST-1 has diverse immunological effects. These include the induction of interleukin 2 receptor expression, interleukin 2 synthesis, proliferation of human T lymphocytes, and stimulation of interleukin 1 synthesis by human monocytes. In the present study, the authors demonstrate that TSST-1 binds with saturation kinetics and with a dissociation constant of 17-43 nM to a single class of binding sites on human mononuclear cells. There was a strong correlation between the number of TSST-1 binding sites and the expression of major histocompatibility complex class II molecules. Affinity chromatography of {sup 125}I-labeled cell membranes over TSST-1-agarose resulted in the recovery of two bands of 35 kDa and 31 kDa that comigrated, respectively, with the {alpha} and {beta} chains of HLA-DR and that could be immunoprecipitated with anti-HLA-DR monoclonal antibodies. Binding of TSST-1 was demonstrated to HLA-DR and HLA-DQ L-cell transfectants. These results indicate that major histocompatibility complex class II molecules represent the major binding site for TSST-1 on human cells.

  4. MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression.

    Science.gov (United States)

    Galbas, Tristan; Steimle, Viktor; Lapointe, Réjean; Ishido, Satoshi; Thibodeau, Jacques

    2012-07-01

    IL-10 is vastly studied for its anti-inflammatory properties on most immune cells. However, it has been reported that IL-10 activates B cells, up-regulates their MHC class II molecules and prevents apoptosis. As MARCH1 was shown to be responsible for the intracellular sequestration of MHC class II molecules in dendritic cells and monocytes in response to IL-10, we set out to clarify the role of this ubiquitin ligase in B cells. Here, we demonstrate in mice that splenic follicular B cells represent the major cell population that up-regulate MHC II molecules in the presence of IL-10. Activation of these cells through TLR4, CD40 or the IL-10 receptor caused the down-regulation of MARCH1 mRNA. Accordingly, B cells from MARCH1-deficient mice do not up-regulate I-A(b) in response to IL-10. In all, our results demonstrate that IL-10 can have opposite effects on MARCH1 regulation in different cell types.

  5. HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

    Science.gov (United States)

    De Leo, C; Castelan, N; Lopez, M; Gonzalez, N; Weckmann, A L; Melin-Aldana, H; Vargas-Alarcon, G; Bordes, J; Alarcon-Segovia, D; Granados, J; Ramirez, E; Lisker, R

    1997-12-01

    We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

  6. Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Harjeet Singh

    Full Text Available Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28 that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC in the presence of interleukin (IL-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT. We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼10(10 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion.

  7. Regulation of T cell response to leishmania antigens by determinants of histocompatibility leukocyte class I and II molecules

    Directory of Open Access Journals (Sweden)

    Bacellar O.

    1998-01-01

    Full Text Available It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-g production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC mAb (W6/32 suppressed lymphocyte proliferation by 90% in cultures stimulated with aCD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-g production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-g levels were suppressed by more than 60%, while in the other 2 cultures IFN-g levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.

  8. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lund, Ole

    2009-01-01

    through presentation of extracellularly derived peptides to helper T cells. Identification of which peptides will bind a given MHC molecule is thus of great importance for the understanding of host-pathogen interactions, and large efforts have been placed in developing algorithms capable of predicting...... this binding event. RESULTS: Here, we present a novel artificial neural network-based method, NN-align that allows for simultaneous identification of the MHC class II binding core and binding affinity. NN-align is trained using a novel training algorithm that allows for correction of bias in the training data...... class II alleles, and is demonstrated to outperform other state-of-the-art MHC class II prediction methods. CONCLUSION: The NN-align method is competitive with the state-of-the-art MHC class II peptide binding prediction algorithms. The method is publicly available at http...

  9. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-07-21

    ... HUMAN SERVICES Food and Drug Administration (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  10. 75 FR 54637 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-09-08

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document for Certain Percutaneous Transluminal Coronary Angioplasty (PTCA) Catheters; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY:...

  11. Treatment of Class II malocclusion with bialveolar protrusion by means of unusual extractions and anchorage mini-implant

    OpenAIRE

    Jong-Moon Chae

    2012-01-01

    INTRODUCTION: Patients with dental Class II bialveolar protrusion are generally treated by extracting the four first premolars or two first and two second premolars, and retracting the anterior teeth. This case report describes the treatment of an adult patient with bialveolar protrusion, a Class II canine and molar relationship, and lip protrusion. METHODS: In this patient, the maxillary right second molar (1.7) had to be extracted due to extensive caries. To create sufficient space to retra...

  12. A single residue change leads to a hydroxylated product from the class II diterpene cyclization catalyzed by abietadiene synthase

    Science.gov (United States)

    Criswell, Jared; Potter, Kevin; Shephard, Freya; Beale, Michael H.; Peters, Reuben J.

    2012-01-01

    Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate. While this reaction typically is terminated via methyl deprotonation to yield copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead. Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a copalyl diphosphate intermediate. Here it is shown that substitution of aspartate for a conserved histidine in the class II active site of abietadiene synthase leads to selective production of 8α-hydroxy-CPP instead, demonstrating striking plasticity. PMID:23167845

  13. Early prevention and intervention of Class II division 1 in growing patients

    Science.gov (United States)

    Keerthi, V. Naga; Kanya, S. Dhivya; Babu, K. Pradeep; Mathew, Anoop; Kumar, A. Nanda

    2016-01-01

    Early screening and diagnosis help in preventing and intercepting the severity of the malocclusion which helps in addressing the esthetic and functional concerns. Growth modulation such as mandibular advancement has been an effective procedure in orthodontics. Mandibular growth advancer (MGA) and PowerScope are gaining popularity recently as these are effective in achieving the mandibular advancement and ease of fabrication, placement, and wear. MGA was fabricated by making the upper and lower splints separately and are placed in the oral cavity by joining the two splints in the new construction bite using cold cure, MGA when worn during growth phase helps in condylar remodeling in the temporomandibular joint thus helps in advancement of the mandible. The proclination of the upper anteriors in Class II division 1 can be moved lingually by activating the labial bow in the splint. Dr. Andy Hayes worked in conjunction with American orthodontics developed PowerScope. PowerScope delivers Class II correction with a combination of patient comfort and ease of use that was unmatched among other appliances. This ready to use chairside solution required no laboratory setup, making for a much quicker, and easier installation process and appointment. PowerScopes high quality, fixed one-piece design requires no patient compliance. These superior qualities of PowerScope help in correction of Class II skeletal growing patient in conjunction with fixed orthodontic therapy. MGA and PowerScope were chosen as a functional appliance for this study, which shows decreased ANB angle and effective mandible length was increased. PMID:27195234

  14. A tensor analysis to evaluate the effect of high-pull headgear on Class II malocclusions.

    Science.gov (United States)

    Ngan, P; Scheick, J; Florman, M

    1993-03-01

    The inaccuracies inherent in cephalometric analysis of treatment effects are well known. The objective of this article is to present a more reliable research tool in the analysis of cephalometric data. Bookstein introduced a dilation function by means of a homogeneous deformation tensor as a method of describing changes in cephalometric data. His article gave an analytic description of the deformation tensor that permits the rapid and highly accurate calculation of it on a desktop computer. The first part of this article describes the underlying ideas and mathematics. The second part uses the tensor analysis to analyze the cephalometric results of a group of patients treated with high-pull activator (HPA) to demonstrate the application of this research tool. Eight patients with Class II skeletal open bite malocclusions in the mixed dentition were treated with HPA. A control sample consisting of eight untreated children with Class II who were obtained from The Ohio State University Growth Study was used as a comparison group. Lateral cephalograms taken before and at the completion of treatment were traced, digitized, and analyzed with the conventional method and tensor analysis. The results showed that HPA had little or no effect on maxillary skeletal structures. However, reduction in growth rate was found with the skeletal triangle S-N-A, indicating a posterior tipping and torquing of the maxillary incisors. The treatment also induced additional deformation on the mandible in a downward and slightly forward direction. Together with the results from the conventional cephalometric analysis, HPA seemed to provide the vertical and rotational control of the maxilla during orthopedic Class II treatment by inhibiting the downward and forward eruptive path of the upper posterior teeth. The newly designed computer software permits rapid analysis of cephalometric data with the tensor analysis on a desktop computer. This tool may be useful in analyzing growth changes for

  15. Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs.

    Directory of Open Access Journals (Sweden)

    Jonathan Massey

    Full Text Available A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 "graded" controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032. When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011. Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.

  16. Purification and characterization of a class II α-Mannosidase from Moringa oleifera seed kernels.

    Science.gov (United States)

    Tejavath, Kiran Kumar; Nadimpalli, Siva Kumar

    2014-10-01

    α-Mannosidase (EC. 3.2.1.114) belonging to class II glycosyl hydrolase family 38 was purified from Moringa oleifera seeds to apparent homogeneity by conventional protein purification methods followed by affinity chromatography on Con A Sepharose and size exclusion chromatography. The purified enzyme is a glycoprotein with 9.3 % carbohydrate and exhibited a native molecular mass of 240 kDa, comprising two heterogeneous subunits with molecular masses of 66 kDa (α-larger subunit) and 55 kDa (β-smaller subunit). Among both the subunits only larger subunit stained for carbohydrate with periodic acid Schiff's staining. The optimum temperature and pH for purified enzyme was 50 °C and pH 5.0, respectively. The enzyme was stable within the pH range of 3.0-7.0. The enzyme was inhibited by EDTA, Hg(2+), Ag(2+), and Cu(2+). The activity lost by EDTA was completely regained by addition of Zn(2+). The purified enzyme was characterized in terms of the kinetic parameters K m (1.6 mM) and V max (2.2 U/mg) using para-nitrophenyl-α-D-mannopyranoside as substrate. The enzyme was very strongly inhibited by swainsonine (SW) at 1 μM concentration a class II α-Mannosidase inhibitor, but not by deoxymannojirimycin (DMNJ). Chemical modification studies revealed involvement of tryptophan at active site. The inhibition by SW and requirement of the Zn(2+) as a metal ion suggested that the enzyme belongs to class II α-Mannosidase.

  17. A randomized controlled 30 years follow up of three conventional resin composites in Class II restorations

    DEFF Research Database (Denmark)

    Pallesen, Ulla; van Dijken, Jan WV

    2015-01-01

    three (one set) as similar as possible Class II restorations of moderate size.After cavity preparation, the three cavities were chosen at random to be restored with twochemical-cured (P10, Miradapt) and one light-cured resin composite (P30). A chemical-curedenamel bonding agent was applied after etching......Objective. The aim of this 30 year randomized controlled study was to evaluate, by intrain-dividual comparisons, the durability of three conventional resin composites in Class IIrestorations. Methods. Each of 30 participants, 21 female and 9 male (mean age 30 years, range 20–43),received at least...... of the enamel. The chemical-cured resincomposites were placed in bulk and the light-cured in increments. One operator placed 99restorations (33 sets). The restorations were evaluated with slightly modified USPHS crite-ria at baseline, 2, 3, 5, 10, 15, 20 and 30 years. Statistical analyses were performed by the...

  18. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha.

    Science.gov (United States)

    Qian, David Z; Kachhap, Sushant K; Collis, Spencer J; Verheul, Henk M W; Carducci, Michael A; Atadja, Peter; Pili, Roberto

    2006-09-01

    Hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a critical role in transcriptional gene activation involved in tumor angiogenesis. A novel class of agents, the histone deacetylase (HDAC) inhibitors, has been shown to inhibit tumor angiogenesis and HIF-1 alpha protein expression. However, the molecular mechanism responsible for this inhibition remains to be elucidated. In the current study, we investigated the molecular link between HIF-1 alpha inhibition and HDAC inhibition. Treatment of the VHL-deficient human renal cell carcinoma cell line UMRC2 with the hydroxamic HDAC inhibitor LAQ824 resulted in a dose-dependent inhibition of HIF-1 alpha protein via a VHL-independent mechanism and reduction of HIF-1 alpha transcriptional activity. HIF-1 alpha inhibition by LAQ824 was associated with HIF-1 alpha acetylation and polyubiquitination. HIF-1 alpha immunoprecipitates contained HDAC activity. Then, we tested different classes of HDAC inhibitors with diverse inhibitory activity of class I versus class II HDACs and assessed their capability of targeting HIF-1 alpha. Hydroxamic acid derivatives with known activity against both class I and class II HDACs were effective in inhibiting HIF-1 alpha at low nanomolar concentrations. In contrast, valproic acid and trapoxin were able to inhibit HIF-1 alpha only at concentrations that are effective against class II HDACs. Coimmunoprecipitation studies showed that class II HDAC4 and HDAC6 were associated with HIF-1 alpha protein. Inhibition by small interfering RNA of HDAC4 and HDAC6 reduced HIF-1 alpha protein expression and transcriptional activity. Taken together, these results suggest that class II HDACs are associated with HIF-1 alpha stability and provide a rationale for targeting HIF-1 alpha with HDAC inhibitors against class II isozymes.

  19. Characterization of structural features controlling the receptiveness of empty class II MHC molecules

    DEFF Research Database (Denmark)

    Rupp, Bernd; Günther, Sebastian; Makhmoor, Talat;

    2011-01-01

    MHC class II molecules (MHC II) play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC...... known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues aQ9 and ßN82. Mutagenesis experiments confirmed that replacement of either one of the two......-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting from the structural knowledge provided by this study....

  20. DNA polymorphism of HLA class II genes in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Morling, Niels; Dalhoff, K; Fugger, L;

    1992-01-01

    We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary......) associated DRB Bgl II 9.1 kilobase (kb) fragment (RR = 2.9; P less than 0.05, 'corrected' P greater than 0.05), the DQA1*0501 associated DQA Taq I 4.8 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05), the DQB1*0201 (DQw2) associated DQB Hin dIII 11.5 kb fragment (RR = 3.1; P less...

  1. Angle Class II, subdivision, with agenesis of mandibular second molars and extrusion of maxillary second molars

    Directory of Open Access Journals (Sweden)

    Rubens Rodrigues Tavares

    2015-04-01

    Full Text Available This clinical case reports the treatment of an Angle Class II malocclusion in a young woman with a balanced face affected by agenesis of second and third mandibular molars and subsequent extrusion of second maxillary molars. The atypical and peculiar occlusal anomaly led to individualized treatment proposed in order to normalize dental malpositions, with subsequent rehabilitation of edentulous areas by means of a multidisciplinary approach. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO in partial fulfillment of the requirements for obtaining the title of certified by the BBO.

  2. Surgical correction of class II skeletal malocclusion in an adult patient

    Directory of Open Access Journals (Sweden)

    Ramakrishnan Balachander

    2014-01-01

    Full Text Available Correction of skeletal deformities in adult patients with orthodontics is limited. Orthognathic surgery is the best option for cases when camouflage treatment is questionable and growth modulation is not possible. This case report illustrates the benefit of the team approach in correcting vertical maxillary excess along with class II skeletal deformity. A cosmetic correction was achieved by superior repositioning of maxilla with LeFort I osteotomy and augmentation genioplasty, along with orthodontic treatment. The patient′s facial appearance was markedly improved along with functional and stable occlusion

  3. The immune function of MHC class II molecules mutated in the putative superdimer interface.

    Science.gov (United States)

    Hayball, John D; Lake, Richard A

    2005-05-01

    Analysis of the crystal structure of human class II (HLA-DR1) molecules suggests that the alphabeta heterodimer may be further ordered as a dimer of heterodimers (superdimer), leading to the hypothesis that T cell receptor dimerisation is a mechanism for initiating signaling events preceding T cell activation. The interface between pairs of molecules is stabilised by both salt bridges, polar and hydrophobic interactions. The residues that form the superdimer interface occur in three areas distinct from the antigen-binding groove. They can be defined as follows: region 1, beta-beta contacts in the helix of the beta1 domain; region 2, alpha-alpha contacts near the alpha 1/alpha2 domain junction and region 3; alpha-beta contacts in the alpha2/beta2 domains adjacent to the plasma membrane. To determine whether salt bridges and polar interactions formed within these regions are involved in the immune function of the murine MHC class II molecule, I-A(b), appropriate residues in both the alpha and beta chain were identified and mutated to uncharged alanine. Cell lines transfected with different combinations of mutated alpha and beta chains were generated and tested for MHC class II expression, peptide binding capabilities, and ability to present antigenic peptide to an OVA-specific T cell hybridoma. With the exception of two residues in region 2, the substitutions tested did not modulate MHC class II expression, or peptide binding function. When tested for ability to present peptide to an antigen-specific T cell hybridoma, with the exception of mutations in region 2, the substitutions did not appear to abrogate the ability of I-A(b) to stimulate the T cells. These results suggest that mutation of residues in region 2 of the putative superdimer interface have a gross effect on the ability of I-A(b) to be expressed on the cell surface. However, abrogation of salt bridges in region 1 and 3 do not influence I-A(b) cell surface expression, peptide binding or ability to

  4. Role of PU.1 in MHC Class II Expression via CIITA Transcription in Plasmacytoid Dendritic Cells.

    Science.gov (United States)

    Miura, Ryosuke; Kasakura, Kazumi; Nakano, Nobuhiro; Hara, Mutsuko; Maeda, Keiko; Okumura, Ko; Ogawa, Hideoki; Yashiro, Takuya; Nishiyama, Chiharu

    2016-01-01

    The cofactor CIITA is a master regulator of MHC class II expression and several transcription factors regulating the cell type-specific expression of CIITA have been identified. Although the MHC class II expression in plasmacytoid dendritic cells (pDCs) is also mediated by CIITA, the transcription factors involved in the CIITA expression in pDCs are largely unknown. In the present study, we analyzed the role of a hematopoietic lineage-specific transcription factor, PU.1, in CIITA transcription in pDCs. The introduction of PU.1 siRNA into mouse pDCs and a human pDC cell line, CAL-1, reduced the mRNA levels of MHC class II and CIITA. When the binding of PU.1 to the 3rd promoter of CIITA (pIII) in CAL-1 and mouse pDCs was analyzed by a chromatin immunoprecipitation assay, a significant amount of PU.1 binding to the pIII was detected, which was definitely decreased in PU.1 siRNA-transfected cells. Reporter assays showed that PU.1 knockdown reduced the pIII promoter activity and that three Ets-motifs in the human pIII promoter were candidates of cis-enhancing elements. By electrophoretic mobility shift assays, it was confirmed that two Ets-motifs, GGAA (-181/-178) and AGAA (-114/-111), among three candidates, were directly bound with PU.1. When mouse pDCs and CAL-1 cells were stimulated by GM-CSF, mRNA levels of PU.1, pIII-driven CIITA, total CIITA, MHC class II, and the amount of PU.1 binding to pIII were significantly increased. The GM-CSF-mediated up-regulation of these mRNAs was canceled in PU.1 siRNA-introduced cells. Taking these results together, we conclude that PU.1 transactivates the pIII through direct binding to Ets-motifs in the promoter in pDCs.

  5. Effects of pulp capping materials on fracture resistance of Class II composite restorations

    OpenAIRE

    2015-01-01

    Objective: The aim of this study was to investigate the effect of cavity design and the type of pulp capping materials on the fracture resistance of Class II composite restorations. Materials and Methods: Sixty freshly extracted, sound molar teeth were selected for the study. A dovetail cavity on the mesio-occlusal and a slot cavity on disto-occlusal surfaces of each tooth were prepared, and the teeth were divided 4 groups which one of them as a control group. The pulp capping materials (Ther...

  6. Post-transplant anti-HLA class II antibodies as risk factor for late kidney allograft failure.

    Science.gov (United States)

    Campos, E F; Tedesco-Silva, H; Machado, P G; Franco, M; Medina-Pestana, J O; Gerbase-DeLima, M

    2006-10-01

    The purpose of this study was to prospectively analyze the relationship between the post-transplant anti-HLA class I and/or class II panel reactive antibodies and graft failure due to chronic allograft nephropathy (CAN). We studied 512 first kidney recipients transplanted at a single center, with a graft functioning for at least 3 years. A single blood sample was collected from each patient for antibody evaluation. The median posttransplant time after blood collection was 4.4 years and did not differ between patients with (n = 91) or without anti-HLA antibodies (n = 421). Female gender, pregnancies and blood transfusions were associated with the presence of anti-HLA class I antibodies. Graft function deterioration was associated with anti-HLA class II antibodies. Multivariate analysis showed independent association for creatinine levels (RR = 7.5), acute rejection (RR = 2.6), recipient male gender (RR = 3.6) and anti-HLA class II antibodies (RR = 2.9) and CAN-associated graft loss. In conclusion, the presence of anti-HLA class II antibodies conferred a risk for graft loss before a decline in renal function and increased the risk of graft failure in patients who already had a decline in graft function. Thus, anti-HLA class II antibody monitoring is a useful tool for the management of long-term kidney recipients.

  7. ACTN3 R577X Genotypes Associate with Class II and Deep Bite Malocclusions

    Science.gov (United States)

    Zebrick, Brian; Teeramongkolgul, Teesit; Nicot, Romain; Horton, Michael J.; Raoul, Gwenael; Ferri, Joel; Vieira, Alexandre R.; Sciote, James J.

    2014-01-01

    Introduction α-actinins are myofibril anchor proteins which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p = 0.002). Conclusion ACTN3 577XX is overrepresented in skeletal class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions. PMID:25439211

  8. 40 CFR Table F-1 to Subpart F of... - Performance Specifications for PM2.5 Class II Equivalent Samplers

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Performance Specifications for PM2.5 Class II Equivalent Samplers F Table F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL..., Subpt. F, Table F-1 Table F-1 to Subpart F of Part 53—Performance Specifications for PM2.5 Class...

  9. HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.

    Directory of Open Access Journals (Sweden)

    Anders Näsman

    Full Text Available HPV-DNA positive (HPVDNA+ oropharyngeal squamous cell carcinoma (OSCC has better clinical outcome than HPV-DNA negative (HPVDNA- OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS, disease-specific survival (DSS and overall survival (OS in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT or radiotherapy (RT alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

  10. 77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-03-19

    ... March 19, 2012 Part II Department of Health and Human Services Food and Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls... SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration...

  11. Correlations between dentoskeletal variables and deep bite in Class II Division 1 individuals

    Directory of Open Access Journals (Sweden)

    Leandro Silva Marques

    2011-02-01

    Full Text Available This study aimed to evaluate the cephalometric pattern of Class II Division 1 individuals with deep bite, and to determine possible correlations between dentoskeletal variables and deep bite. Comparisons were also made between genders and cases that were to be treated both with and without premolar extraction. A total of 70 lateral cephalograms were used, from both male (n = 35 and female (n = 35 individuals with an average age of 11.6 years, who simultaneously presented with ANB > 5º and overbite > 4 mm. Statistical analysis involved parametric (t-test and non-parametric (Mann-Whitney tests for independent samples, as well as the Spearman correlation test (p < 0.05. The values of Go-Me, Ar-Pog, PM-1 and PM-CMI were higher in males (p < 0.05. However, no significant differences were found among the averages of the cephalometric measurements when the sample was divided by treatment with and without extraction. Deep bite was positively correlated to the PM-1 and SNA measurements, and negatively correlated to the Go-Me, Ar-Pog, SNB and SNGoMe measurements. The main factors associated with the determination of deep bite in Angle's Class II Division 1 cases were: greater lower anterior dentoalveolar growth and/or lower incisor extrusion, horizontal growth pattern, maxillary protrusion and mandibular retrusion.

  12. Comparison of 2 modifications of the twin-block appliance in matched Class II samples.

    Science.gov (United States)

    Parkin, N A; McKeown, H F; Sandler, P J

    2001-06-01

    The purpose of this study was to compare the skeletal and dental changes contributing to Class II correction with 2 modifications of the Twin-block appliance: Twin-block appliances that use a labial bow (TB1) and Twin-block appliances that incorporate high-pull headgear and torquing spurs on the maxillary central incisors (TB2). After pretreatment equivalence was established, a total of 36 consecutively treated patients with the TB1 modification were compared with 27 patients treated with the TB2 modification. Both samples were treated in the same hospital department and the same technician made all the appliances. The cephalostat, digitizing package, and statistical methods were common to both groups. The results demonstrated that the addition of headgear to the appliance resulted in effective vertical and sagittal control of the maxillary complex and thus maximized the Class II skeletal correction in the TB2 sample. Use of the torquing springs resulted in less retroclination of the maxillary incisors in the TB2 sample when compared with the TB1 sample; however, this difference did not reach the level of statistical significance.

  13. Transverse craniofacial dimensions in Angle Class II, Division 1 malocclusion according to breathing mode

    Directory of Open Access Journals (Sweden)

    Agda Rísia David Pinto Coelho

    2010-03-01

    Full Text Available The aim of this longitudinal study was to assess the relation between the transverse craniofacial dimensions of subjects with Class II, Division 1 malocclusion and the breathing mode presented by them. Forty Angle Class II, Division 1 malocclusion subjects of both genders participated in the study, 23 of which were predominantly nose breathers and 17 were predominantly mouth breathers. The mean age ranged from 10 years and 9 months to 14 years - Age range 1; and from 13 years and 4 months to 16 years and 6 months - Age range 2. Measurements of six transverse craniofacial dimensions were performed in P-A teleradiographs: Total Sphenoid, Total Zygomatic, Total Nasal Cavity, Total Maxilla, Total Mastoid and Total Antegonion. The transversal craniofacial dimensions were measured and compared in both groups at age ranges 1 and 2. The longitudinal assessment of age ranges 1 and 2 showed that there was no statistically significant influence of the breathing mode on the craniofacial dimensions evaluated, or on the alteration of these dimensions. Breathing mode had no influence on craniofacial development in the sample studied.

  14. Morphological changes of the facial skeleton in Class II/1 patients treated with orthodontic functional appliances

    Directory of Open Access Journals (Sweden)

    Dana Festila

    2014-01-01

    Full Text Available Aim: The aim of this study was to investigate, using lateral cephalometry, the skeletal changes in maxillary bones induced through functional jaw orthopedic therapy. 30 patients with class II division 1 malocclusion and average age of 10.4 years were included in the study. Material and Methods: Cephalometric data were analyzed with the following methods: Burstone, McNamara, Rickets, Tweed and Wits and treatment changes were evaluated overlapping the lateral cephalograms on cranial base with sella registered. Results: The results showed reduced over-jet in average with 2.46 mm, mandibular advancement with a mean value of 2.72 mm and increasing of the total mandibular length with a mean value of 4.17 mm. Although we found an inhibiting in the anterior development of the maxilla with an average of 1.57 degree, the decrease of the anterior-posterior discrepancy was due especially to the mandible. Conclusions: It can be concluded that functional appliances were effective in correcting class II malocclusion. Changes of the position and mandible′s length determined improved facial profile but did not correct it completely because of the chin that moved not only anterior but also downward, as a result of vertical ramus growth.

  15. Genomic analysis identifies class II mismatches in serologically DR-compatible human renal allografts.

    Science.gov (United States)

    Bushell, A; Wood, K J; Morris, P J

    1988-11-01

    Many studies, including those from our own center, have shown that matching the donor and recipient for HLA-DR antigens has a beneficial effect on the outcome of cadaveric renal transplantation. However, cases of irreversible graft rejection are sometimes seen in patients who have received an HLA-DR-compatible kidney, suggesting that serologic compatibility for HLA-DR may not always ensure reduced alloreactivity toward the graft. We have examined a number of recipients and their serologically DR-compatible cadaveric donors by Southern blotting and hybridization with locus specific HLA class II probes in order to determine whether in these patients there were class II mismatches that had been undetected by serology. The results show that the analysis of DR beta restriction fragment patterns does little more than complement and confirm the serologic identification of HLA-DR. Hybridization with DQ alpha and DQ beta probes, however, significantly extends the number of DQ specificities that can be detected and suggests that DQ mismatches in DR-compatible donor-recipient pairs may be more common than previously supposed, although it is not possible to draw any conclusions on the influence of DQ incompatibilities in the presence of DR compatibility on graft outcome.

  16. Prediction of positive food effect: Bioavailability enhancement of BCS class II drugs.

    Science.gov (United States)

    Raman, Siddarth; Polli, James E

    2016-06-15

    High-throughput screening methods have increased the number of poorly water-soluble, highly permeable drug candidates. Many of these candidates have increased bioavailability when administered with food (i.e., exhibit a positive food effect). Food is known to impact drug bioavailability through a variety of mechanisms, including drug solubilization and prolonged gastric residence time. In vitro dissolution media that aim to mimic in vivo gastrointestinal (GI) conditions have been developed to lessen the need for fed human bioequivalence studies. The objective of this work was to develop an in vitro lipolysis model to predict positive food effect of three BCS Class II drugs (i.e., danazol, amiodarone and ivermectin) in previously developed lipolysis media. This in vitro lipolysis model was comparatively benchmarked against FeSSIF and FaSSIF media that were modified for an in vitro lipolysis approach, as FeSSIF and FaSSIF are widely used in in vitro dissolution studies. The in vitro lipolysis model accurately predicted the in vivo positive food effect for three model BCS class II drugs. The in vitro lipolysis model has potential use as a screening test of drug candidates in early development to assess positive food effect.

  17. Search for class II methanol masers at 23.1 GHz

    CERN Document Server

    Cragg, D M; Caswell, J L; Ellingsen, S P; Godfrey, P D

    2004-01-01

    In the early days of methanol maser discoveries the 9(2)-10(1) A+ transition at 23.1 GHz was found to exhibit maser characteristics in the northern star-forming region W3(OH), and probable maser emission in two other sources. Attention subsequently turned to the 6.6-GHz 5(1)-6(0) A+ methanol maser transition, which has proved a valuable tracer of early high-mass star formation. We have undertaken a new search for 23.1-GHz methanol masers in 50 southern star formation regions using the Parkes radiotelescope. The target sources all exhibit class II methanol maser emission at 6.6 GHz, with 20 sources also displaying maser features in the 107.0-GHz 3(1)-4(0) A+ methanol line. Strong emission at 23.1 GHz in NGC 6334F was confirmed, but no emission was detected in the remaining sources. Thus the 23.1-GHz methanol masers are rare. A maser model in which methanol molecules are pumped to the second torsionally excited state by radiation from warm dust can account for class II maser activity in all the transitions in w...

  18. IMPORTANCE OF RESEARCH HLA ANTIBODIES CLASS I AND II, AND MICA ANTIBODIES IN KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2011-01-01

    Full Text Available The purpose of this study was to investigate the occurrence of HLA and MICA antibodies in patients from the waiting list for kidney transplantation and their influence on the course of post-transplant period. Determination of HLA antibodies class I and II, and MICA antibodies was performed on a platform of Luminex (xMAP-tech- nology using sets LABScreen ONE LAMBDA (U.S.. A total of 156 patients from the waiting list for kidney transplantation. Revealed the presence of HLA and MICA antibodies in the serum of 31.4% of patients. Regraf- ted patients increased the content of antibodies to the antigens of HLA system was noted in 88.2% of cases, 47% met the combination of antibodies to the I, II classes and MICA. In patients awaiting first kidney transplantation, HLA and MICA antibodies were determined in 23.7% of cases. The presence of pretransplant HLA and MICA antibodies had a significant influence on the course of post-transplant period. Patients with the presence of HLA and MICA in 50% of cases delayed graft function. Sessions of plasmapheresis can reduce the concentration of HLA and MICA antibodies on average by 61.1%. 

  19. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens;

    2014-01-01

    sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast......JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV...... for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR...

  20. Clinical effects of fixed functional Herbst appliance in the treatment of class II/1 malocclusion

    Directory of Open Access Journals (Sweden)

    Nedeljković Nenad

    2009-01-01

    Full Text Available Introduction. Sagittal mandible deficiency is the most common cause of skeletal Class II malocclusion. Treatment objective is to stimulate sagittal mandible growth. Fixed functional Herbst appliance use is beneficial for shortening the time required for treatment and does not depend on patient compliance. Case outline. A 13-year-old girl was referred to the Clinic of Orthodontics, School of Dentistry in Belgrade following previous unsuccessful treatment of her skeletal Class II malocclusion using an activator. The patient's poor cooperation had led to failure of the treatment. Patient was subjected to the Herbst treatment for 6 months followed by fixed appliance for another 8 months. Lateral cephalograms before and after the treatment was performed. The remodelation of condylar and fossal articulation was assessed by superimposition of pre- and post-treatment temporomandibular joint tomograms. The promotion of oral hygiene and fluoride use was performed because orthodontic treatment carries a high caries risk and risk for periodontal disease. Skeletal and dental changes were observed after treatment (correction [Max+Mand]: molar relation 7 mm, overjet 8 mm, skeletal relation 5 mm, molars 2 mm, incisors 3 mm. Combination of Herbst and fixed appliances was effective in the treatment of dental and skeletal irregularities for a short period of time. Conclusion . In the retention period, 14 months after treatment, occlusal stability exists. Follow-up care in oral prevention is based on regular recalls at the dental office and supervision at home by the parents.

  1. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction

    Directory of Open Access Journals (Sweden)

    Lund Ole

    2009-09-01

    Full Text Available Abstract Background The major histocompatibility complex (MHC molecule plays a central role in controlling the adaptive immune response to infections. MHC class I molecules present peptides derived from intracellular proteins to cytotoxic T cells, whereas MHC class II molecules stimulate cellular and humoral immunity through presentation of extracellularly derived peptides to helper T cells. Identification of which peptides will bind a given MHC molecule is thus of great importance for the understanding of host-pathogen interactions, and large efforts have been placed in developing algorithms capable of predicting this binding event. Results Here, we present a novel artificial neural network-based method, NN-align that allows for simultaneous identification of the MHC class II binding core and binding affinity. NN-align is trained using a novel training algorithm that allows for correction of bias in the training data due to redundant binding core representation. Incorporation of information about the residues flanking the peptide-binding core is shown to significantly improve the prediction accuracy. The method is evaluated on a large-scale benchmark consisting of six independent data sets covering 14 human MHC class II alleles, and is demonstrated to outperform other state-of-the-art MHC class II prediction methods. Conclusion The NN-align method is competitive with the state-of-the-art MHC class II peptide binding prediction algorithms. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCII-2.0.

  2. Rational Design Synthesis and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases

    Energy Technology Data Exchange (ETDEWEB)

    R Daher; M Coincon; M Fonvielle; P Gest; M Guerin; M Jackson; J Sygusch; M Therisod

    2011-12-31

    We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows Ki against class II Fbas from various pathogens in the nM range, with very high selectivity (up to 105). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.

  3. Treatment of Class II high angle malocclusions with the Herbst appliance: a cephalometric investigation.

    Science.gov (United States)

    Schiavoni, R; Grenga, V; Macri, V

    1992-11-01

    The purpose of this study was to examine the results of treatment of Class II malocclusions by using two different designs of the Herbst appliance. Cephalometric records from lateral headplates of 19 consecutively treated Class II cases were evaluated. The headplates were taken before and after the treatment stage in which the Herbst appliance was used. The patients were divided into two groups: the first group, normohypodivergent, was treated with the Herbst appliance attached to bands; the second group, hyperdivergent, was treated with the Herbst appliance attached to acrylic splints in which a high-pull headgear was also used. The results were compared between these groups and with a control group age-matched from Bolton standards to match the changes in the Herbst samples against what might be expected in case of normal growth during similar periods of time. The results of the investigation revealed the following: (1) 9 months of treatment resulted in Class I dental arch relationships in all 19 cases; (2) the Herbst appliance attached to bands did not significantly modify the vertical growth pattern of the normohypodivergent patients; and (3) in hyperdivergent patients, the use of a Herbst appliance attached to acrylic splints in conjunction with the use of a high-pull headgear allowed a better control of the vertical dimension, as assessed by the cephalometric parameters (FA, FMA, Go-Gn-SN). The clinician should be aware of the different dentofacial changes induced in the vertical plane by different designs of the Herbst appliance to better program treatment strategy.

  4. The Novel Toll-Like Receptor 2 Agonist SUP3 Enhances Antigen Presentation and T Cell Activation by Dendritic Cells

    Science.gov (United States)

    Guo, Xueheng; Wu, Ning; Shang, Yingli; Liu, Xin; Wu, Tao; Zhou, Yifan; Liu, Xin; Huang, Jiaoyan; Liao, Xuebin; Wu, Li

    2017-01-01

    Dendritic cells (DCs) are highly specialized antigen-presenting cells that play crucial roles in innate and adaptive immunity. Previous studies suggested that Toll-like receptor (TLR) agonists could be used as potential adjuvants, as activation of TLRs can boost DC-induced immune responses. TLR2 agonists have been shown to enhance DC-mediated immune responses. However, classical TLR2 agonists such as Pam3CSK4 are not stable enough in vivo, which limits their clinical applications. In this study, a novel structurally stable TLR2 agonist named SUP3 was designed. Functional analysis showed that SUP3 induced much stronger antitumor response than Pam3CSK4 by promoting cytotoxic T lymphocytes activation in vivo. This effect was achieved through the following mechanisms: SUP3 strongly enhanced the ability of antigen cross-presentation by DCs and subsequent T cell activation. SUP3 upregulated the expression of costimulatory molecules on DCs and increased antigen deposition in draining lymph nodes. More interestingly, SUP3 induced less amount of pro-inflammatory cytokine production in vivo compared to other TLR agonists such as lipopolysaccharide. Taken together, SUP3 could serve as a novel promising immune adjuvant in vaccine development and immune modulations.

  5. Original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice.

    Directory of Open Access Journals (Sweden)

    Valérie Abadie

    Full Text Available BACKGROUND: Obtaining a certain multi-functionality of cellular immunity for the control of infectious diseases is a burning question in immunology and in vaccine design. Early events, including antigen shuttling to secondary lymphoid organs and recruitment of innate immune cells for adaptive immune response, determine host responsiveness to antigens. However, the sequence of these events and their impact on the quality of the immune response remain to be elucidated. Here, we chose to study Modified Vaccinia virus Ankara (MVA which is now replacing live Smallpox vaccines and is proposed as an attenuated vector for vaccination strategies against infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vivo mechanisms triggered following intradermal (i.d. and intramuscular (i.m. Modified Vaccinia virus Ankara (MVA administration. We demonstrated significant differences in the antigen shuttling to lymphoid organs by macrophages (MPhis, myeloid dendritic cells (DCs, and neutrophils (PMNs. MVA i.d. administration resulted in better antigen distribution and more sustained antigen-presenting cells (APCs recruitment into draining lymph nodes than with i.m. administration. These APCs, which comprise both DCs and MPhis, were differentially involved in T cell priming and shaped remarkably the quality of cytokine-producing virus-specific T cells according to the entry route of MVA. CONCLUSIONS/SIGNIFICANCE: This study improves our understanding of the mechanisms of antigen delivery and their consequences on the quality of immune responses and provides new insights for vaccine development.

  6. Structure-Function Assessment of Mannosylated Poly(β-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery.

    Science.gov (United States)

    Jones, Charles H; Chen, Mingfu; Gollakota, Akhila; Ravikrishnan, Anitha; Zhang, Guojian; Lin, Sharon; Tan, Myles; Cheng, Chong; Lin, Haiqing; Pfeifer, Blaine A

    2015-05-11

    Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure-function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure-function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (∼300 nm) with moderate charge densities (structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.

  7. IL-4 abrogates TH17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells

    Science.gov (United States)

    Guenova, Emmanuella; Skabytska, Yuliya; Hoetzenecker, Wolfram; Weindl, Günther; Sauer, Karin; Tham, Manuela; Kim, Kyu-Won; Park, Ji-Hyeon; Seo, Ji Hae; Ignatova, Desislava; Cozzio, Antonio; Levesque, Mitchell P.; Volz, Thomas; Köberle, Martin; Kaesler, Susanne; Thomas, Peter; Mailhammer, Reinhard; Ghoreschi, Kamran; Schäkel, Knut; Amarov, Boyko; Eichner, Martin; Schaller, Martin; Clark, Rachael A.; Röcken, Martin; Biedermann, Tilo

    2015-01-01

    Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12–producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4–mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/TH17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/TH17 responses without blocking IL-12/TH1, selective IL-4–mediated IL-23/TH17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12–dependent TH1 responses. PMID:25646481

  8. MAXILLARY INCISOR TRAUMA IN PATIENTS WITH CLASS II DIVISION 1 DENTAL MALOCCLUSION: ASSOCIATED FACTORS

    Directory of Open Access Journals (Sweden)

    Elif Yaman DOSDOĞRU

    2017-01-01

    Full Text Available Purpose: The aim of this study was to assess the association between the presence of maxillary incisor trauma (MIT with age, gender, dentition type, the degree of overjet (OJ, lip form, respiratory type and dental arch form in patients with Class II division 1 dental malocclusion. Subjects and Methods: 256 patients (mean age: 15.80 ± 2.2 were included in this study. The patients’ gender, dentition type, superior lip form, dental arch form and respiratory type were recorded. Participants were divided into four groups according to the severity of OJ: 3.5 mm II ≤ 6 mm with incompetent lip, 6 mmClass II division 1 malocclusion.

  9. Selection and trans-species polymorphism of major histocompatibility complex class II genes in the order Crocodylia.

    Directory of Open Access Journals (Sweden)

    Weerachai Jaratlerdsiri

    Full Text Available Major Histocompatibility Complex (MHC class II genes encode for molecules that aid in the presentation of antigens to helper T cells. MHC characterisation within and between major vertebrate taxa has shed light on the evolutionary mechanisms shaping the diversity within this genomic region, though little characterisation has been performed within the Order Crocodylia. Here we investigate the extent and effect of selective pressures and trans-species polymorphism on MHC class II α and β evolution among 20 extant species of Crocodylia. Selection detection analyses showed that diversifying selection influenced MHC class II β diversity, whilst diversity within MHC class II α is the result of strong purifying selection. Comparison of translated sequences between species revealed the presence of twelve trans-species polymorphisms, some of which appear to be specific to the genera Crocodylus and Caiman. Phylogenetic reconstruction clustered MHC class II α sequences into two major clades representing the families Crocodilidae and Alligatoridae. However, no further subdivision within these clades was evident and, based on the observation that most MHC class II α sequences shared the same trans-species polymorphisms, it is possible that they correspond to the same gene lineage across species. In contrast, phylogenetic analyses of MHC class II β sequences showed a mixture of subclades containing sequences from Crocodilidae and/or Alligatoridae, illustrating orthologous relationships among those genes. Interestingly, two of the subclades containing sequences from both Crocodilidae and Alligatoridae shared specific trans-species polymorphisms, suggesting that they may belong to ancient lineages pre-dating the divergence of these two families from the common ancestor 85-90 million years ago. The results presented herein provide an immunogenetic resource that may be used to further assess MHC diversity and functionality in Crocodylia.

  10. Selection and trans-species polymorphism of major histocompatibility complex class II genes in the order Crocodylia.

    Science.gov (United States)

    Jaratlerdsiri, Weerachai; Isberg, Sally R; Higgins, Damien P; Miles, Lee G; Gongora, Jaime

    2014-01-01

    Major Histocompatibility Complex (MHC) class II genes encode for molecules that aid in the presentation of antigens to helper T cells. MHC characterisation within and between major vertebrate taxa has shed light on the evolutionary mechanisms shaping the diversity within this genomic region, though little characterisation has been performed within the Order Crocodylia. Here we investigate the extent and effect of selective pressures and trans-species polymorphism on MHC class II α and β evolution among 20 extant species of Crocodylia. Selection detection analyses showed that diversifying selection influenced MHC class II β diversity, whilst diversity within MHC class II α is the result of strong purifying selection. Comparison of translated sequences between species revealed the presence of twelve trans-species polymorphisms, some of which appear to be specific to the genera Crocodylus and Caiman. Phylogenetic reconstruction clustered MHC class II α sequences into two major clades representing the families Crocodilidae and Alligatoridae. However, no further subdivision within these clades was evident and, based on the observation that most MHC class II α sequences shared the same trans-species polymorphisms, it is possible that they correspond to the same gene lineage across species. In contrast, phylogenetic analyses of MHC class II β sequences showed a mixture of subclades containing sequences from Crocodilidae and/or Alligatoridae, illustrating orthologous relationships among those genes. Interestingly, two of the subclades containing sequences from both Crocodilidae and Alligatoridae shared specific trans-species polymorphisms, suggesting that they may belong to ancient lineages pre-dating the divergence of these two families from the common ancestor 85-90 million years ago. The results presented herein provide an immunogenetic resource that may be used to further assess MHC diversity and functionality in Crocodylia.

  11. Characterization of structural features controlling the receptiveness of empty class II MHC molecules.

    Directory of Open Access Journals (Sweden)

    Bernd Rupp

    Full Text Available MHC class II molecules (MHC II play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC molecule. Non-receptiveness hinders the efficient loading of new antigens onto the empty MHC II. However, the mechanisms driving the formation of the peptide inaccessible state are not well understood. Here, a combined approach of experimental site-directed mutagenesis and computational modeling is used to reveal structural features underlying "non-receptiveness." Molecular dynamics simulations of the human MHC II HLA-DR1 suggest a straightening of the α-helix of the β1 domain during the transition from the open to the non-receptive state. The movement is mostly confined to a hinge region conserved in all known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues αQ9 and βN82. Mutagenesis experiments confirmed that replacement of either one of the two residues by alanine renders the protein highly susceptible. Notably, loading enhancement was also observed when the mutated MHC II molecules were expressed on the surface of fibroblast cells. Altogether, structural features underlying the non-receptive state of empty HLA-DR1 identified by theoretical means and experiments revealed highly conserved residues critically involved in the receptiveness of MHC II. The atomic details of rearrangements of the peptide-binding groove upon peptide loss provide insight into structure and dynamics of empty MHC II molecules and may foster rational approaches to interfere with non-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting

  12. A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes.

    Science.gov (United States)

    Dijkstra, Johannes Martinus; Katagiri, Takayuki; Hosomichi, Kazuyoshi; Yanagiya, Kazuyo; Inoko, Hidetoshi; Ototake, Mitsuru; Aoki, Takashi; Hashimoto, Keiichiro; Shiina, Takashi

    2007-04-01

    Most of the previously studied teleost MHC class I molecules can be classified into two broad lineages: "U" and "Z/ZE." However, database reports on genes in cyprinid and salmonid fishes show that there is a third major lineage, which lacks detailed analysis so far. We designated this lineage "L" because of an intriguing linkage characteristic. Namely, one zebrafish L locus is closely linked with MHC class II loci, despite the extensively documented nonlinkage of teleost class I with class II. The L lineage consists of highly variable, nonclassical MHC class I genes, and has no apparent orthologues outside teleost fishes. Characteristics that distinguish the L lineage from most other MHC class I are (1) absence of two otherwise highly conserved tryptophan residues W51 and W60 in the alpha1 domain, (2) a low GC content of the alpha1 and alpha2 exons, and (3) an HINLTL motif including a possible glycosylation site in the alpha3 domain. In rainbow trout (Oncorhynchus mykiss) we analyzed several intact L genes in detail, including their genomic organization and transcription pattern. The gene Onmy-LAA is quite different from the genes Onmy-LBA, Onmy-LCA, Onmy-LDA, and Onmy-LEA, while the latter four are similar and categorized as "Onmy-LBA-like." Whereas the Onmy-LAA gene is organized like a canonical MHC class I gene, the Onmy-LBA-like genes are processed and lack all introns except intron 1. Onmy-LAA is predominantly expressed in the intestine, while the Onmy-LBA-like transcripts display a rather homogeneous tissue distribution. To our knowledge, this is the first description of an MHC class I lineage with multiple copies of processed genes, which are intact and transcribed. The present study significantly improves the knowledge of MHC class I variation in teleosts.

  13. Articulación de fones en individuos clase esqueletal I,II y III Speech patterns in skeletal class I, II and III subjects

    Directory of Open Access Journals (Sweden)

    Pía Villanueva

    2009-09-01

    Full Text Available OBJETIVO: determinar los patrones de articulación de fones consonánticos en sujetos de habla española chilena clases I, II y III esqueletal; comparar las diferencias fonéticas que existan entre clases esqueletales. MÉTODOS: se seleccionaron 54 individuos que cumplían con los criterios de inclusión determinados mediante un examen clínico intraoral y a través del análisis de Ricketts, y se conformaron los grupos de estudio de pacientes clases esqueletales I, II y III. Se les realizó un examen fonoarticulatorio estandarizado para determinar los fones modificados y el patrón articulatorio compensatorio realizado. RESULTADOS: se observaron cambios en el punto de articulación de fones consonánticos en las tres clases esqueletales, con diferencias significativas en los grupos de fones anteriores y medios entre pacientes clases I y II, sólo en el grupo de los fones anteriores entre pacientes I y III. Entre pacientes clases II y III no se observaron diferencias significativas. Se reportan modificaciones y compensaciones cualitativamente distintas entre las clases esqueletales. CONCLUSIONES: en relación a pacientes clase I, los pacientes clase II o III, presentan distinto grado de modificación en el punto de articulación de fones consonánticos. Las diferencias observadas se relacionan con los patrones esqueletales propios de cada clase.PURPOSE: to determine the consonant phonemes articulation patterns in Chilean skeletal class I, II and III Spanish speakers and compare their phonetic differences. METHODS: fifty-four skeletal class I, II and III subjects were selected, based on intraoral clinical examination and Ricketts cephalometric analysis, constituting the study groups. A standardized phonoarticulatory test was applied to each patient to determine the modified phonemes and their compensatory patterns. RESULTS: the findings indicate changes in articulation in all three groups. Significant differences were found in anterior and medium

  14. MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data.

    Science.gov (United States)

    Papassavas, E C; Spyropoulou-Vlachou, M; Papassavas, A C; Schipper, R F; Doxiadis, I N; Stavropoulos-Giokas, C

    2000-06-01

    In the present study, DNA typing for HLA-A, C, B, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, and DPB1 was performed for 246 healthy, unrelated Greek volunteers of 20-59 years of age. Phenotype, genotype frequencies, Hardy-Weinberg equilibrium fit, and 3-locus haplotype frequencies for HLA-A, C, B, HLA-A, B, DRB1, HLA-DRB1, DQA1, DQB1, and HLA-DRB1, DQB1, DPB1 were calculated. Furthermore, linkage disequilibrium, deltas, relative deltas and p-values for significance of the deltas were defined. The population studied is in Hardy-Weinberg equilibrium, and many MHC haplotypes are in linkage disequilibrium. The most frequent specificities were HLA-A*02 (phenotype frequency = 44.3%) followed by HLA-A*24 (27.2%), HLA-B*51 (28.5%), HLA-B*18 (26.8%) and HLA-B*35 (26.4%) and HLA-Cw*04 (30.1%) and HLA-Cw*12 (26.8%). The most frequent MHC class II alleles were HLA-DRB1*1104 (34.1%), HLA-DQB1*0301 (54.5%) and HLA-DPB1*0401 with a phenotype frequency of 59.8%. The most prominent HLA-A, C, B haplotypes were HLA-A*24, Cw*04, B*35, and HLA-A*02, Cw*04, B*35, each of them observed in 21/246 individuals. The most frequent HLA-A, B, DRB1 haplotype was HLA-A*02, B*18, DRB1*1104 seen in 20/246 individuals, while the haplotype HLA-DRB1*1104, DQB1*0301, DPB1*0401 was found in 49/246 individuals. Finally, the haplotype DRB1*1104, DQA1*0501, DQB1*0301 was observed in 83/246 individuals. These results can be used for the estimation of the probability of finding a suitable haplotypically identical related or unrelated stem cell donor for patients of Greek ancestry. In addition, they can be used for HLA and disease association studies, genetic distance studies in the Balkan and Mediterranean area, paternity cases, and matching probability calculations for the optimal allocation of kidneys in Greece.

  15. TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells.

    Science.gov (United States)

    Haruta, M; Tomita, Y; Yuno, A; Matsumura, K; Ikeda, T; Takamatsu, K; Haga, E; Koba, C; Nishimura, Y; Senju, S

    2013-05-01

    We previously reported a method to generate dendritic cell (DC)-like antigen-presenting cells (APC) from human induced pluripotent stem (iPS) cells. However, the method is relatively complicated and laborious. In the current study, we attempted to establish a method through which we could obtain a large number of functional APC with a simple procedure. We transduced iPS cell-derived CD11b(+) myeloid cells with genes associated with proliferative or anti-senescence effects, enabling the cells to propagate for more than 4 months in a macrophage colony-stimulating factor (M-CSF)-dependent manner while retaining their capacity to differentiate into functional APC. We named these iPS cell-derived proliferating myeloid cells 'iPS-ML', and the iPS-ML-derived APC 'ML-DC'. In addition, we generated TAP2-deficient iPS cell clones by zinc finger nuclease-aided targeted gene disruption. TAP2-deficient iPS cells and iPS-ML avoided recognition by pre-activated allo-reactive CD8(+) T cells. TAP2-deficient ML-DC expressing exogenously introduced HLA-A2 genes stimulated HLA-A2-restricted MART-1-specific CD8(+) T cells obtained from HLA-A2-positive allogeneic donors, resulting in generation of MART-1-specific cytotoxic T lymphocyte (CTL) lines. TAP-deficient iPS-ML introduced with various HLA class I genes may serve as an unlimited source of APC for vaccination therapy. If administered into allogeneic patients, ML-DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and, after that, be completely eliminated. Based on the present study, we propose an APC-producing system that is simple, safe and applicable to all patients irrespective of their HLA types.

  16. mRNA Structural constraints on EBNA1 synthesis impact on in vivo antigen presentation and early priming of CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Judy T Tellam

    2014-10-01

    Full Text Available Recent studies have shown that virally encoded mRNA sequences of genome maintenance proteins from herpesviruses contain clusters of unusual structural elements, G-quadruplexes, which modulate viral protein synthesis. Destabilization of these G-quadruplexes can override the inhibitory effect on self-synthesis of these proteins. Here we show that the purine-rich repetitive mRNA sequence of Epstein-Barr virus encoded nuclear antigen 1 (EBNA1 comprising G-quadruplex structures, limits both the presentation of MHC class I-restricted CD8(+ T cell epitopes by CD11c(+ dendritic cells in draining lymph nodes and early priming of antigen-specific CD8(+ T-cells. Destabilization of the G-quadruplex structures through codon-modification significantly enhanced in vivo antigen presentation and activation of virus-specific T cells. Ex vivo imaging of draining lymph nodes by confocal microscopy revealed enhanced antigen-specific T-cell trafficking and APC-CD8(+ T-cell interactions in mice primed with viral vectors encoding a codon-modified EBNA1 protein. More importantly, these antigen-specific T cells displayed enhanced expression of the T-box transcription factor and superior polyfunctionality consistent with the qualitative impact of translation efficiency. These results provide an important insight into how viruses exploit mRNA structure to down regulate synthesis of their viral maintenance proteins and delay priming of antigen-specific T cells, thereby establishing a successful latent infection in vivo. Furthermore, targeting EBNA1 mRNA rather than protein by small molecules or antisense oligonucleotides will enhance EBNA1 synthesis and the early priming of effector T cells, to establish a more rapid immune response and prevent persistent infection.

  17. The ESAT-6 Protein of Mycobacterium tuberculosis Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage

    Science.gov (United States)

    Parveen, Nazia; Jha, Vishwanath; Valluri, Vijaya Lakshmi; Ghosh, Sudip; Mukhopadhyay, Sangita

    2014-01-01

    ESAT-6, an abundantly secreted protein of Mycobacterium tuberculosis (M. tuberculosis) is an important virulence factor, inactivation of which leads to reduced virulence of M. tuberculosis. ESAT-6 alone, or in complex with its chaperone CFP-10 (ESAT-6:CFP-10), is known to modulate host immune responses; however, the detailed mechanisms are not well understood. The structure of ESAT-6 or ESAT-6:CFP-10 complex does not suggest presence of enzymatic or DNA-binding activities. Therefore, we hypothesized that the crucial role played by ESAT-6 in the virulence of mycobacteria could be due to its interaction with some host cellular factors. Using a yeast two-hybrid screening, we identified that ESAT-6 interacts with the host protein beta-2-microglobulin (β2M), which was further confirmed by other assays, like GST pull down, co-immunoprecipitation and surface plasmon resonance. The C-terminal six amino acid residues (90–95) of ESAT-6 were found to be essential for this interaction. ESAT-6, in complex with CFP-10, also interacts with β2M. We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters β2M to inhibit cell surface expression of MHC-I-β2M complexes, resulting in downregulation of class I-mediated antigen presentation. Interestingly, the ESAT-6:β2M complex could be detected in pleural biopsies of individuals suffering from pleural tuberculosis. Our data highlight a novel mechanism by which M. tuberculosis may undermine the host adaptive immune responses to establish a successful infection. Identification of such novel interactions may help us in designing small molecule inhibitors as well as effective vaccine design against tuberculosis. PMID:25356553

  18. Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

    Science.gov (United States)

    Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

    2016-01-01

    Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This

  19. Extracellular acidosis promotes neutrophil transdifferentiation to MHC class II-expressing cells.

    Science.gov (United States)

    Pliyev, Boris K; Sumarokov, Alexander B; Buriachkovskaia, Lyudmila I; Menshikov, Mikhail

    2011-01-01

    Inflammation in peripheral tissues is usually associated with local acidosis. In the present study, we demonstrate that extracellular acidification enhances GM-CSF- and IFN-γ-induced expression of HLA-DR, CD80 and CD86 in human neutrophils (neutrophil transdifferentiation), and potentiates antigen-capturing capacities (both endocytosis and phagocytosis) of the transdifferentiated cells. Furthermore, in acidic conditions the transdifferentiated neutrophils have stronger antigen-presenting capacity, inducing more intense proliferation of autologous T lymphocytes in the presence of staphylococcal enterotoxin A. Thus, extracellular acidosis can represent a factor that promotes neutrophil transdifferentiation and potentiates the functional abilities of the transdifferentiated cells in inflammatory foci in vivo.

  20. Probing the Evolution of Massive Young Stellar Objects using Weak Class II 6.7GHz Methanol Maser Emission

    Science.gov (United States)

    Ludwig, Bethany Ann; Cunningham, Nichol

    2017-01-01

    We present results from an investigation of class II 6.7GHz methanol masers towards four Massive Young Stellar Objects (MYSOs). The sources, selected from the Red MSX Source (RMS) Survey (Lumsden et al. 2013), were previously understood to be non-detections for class II methanol maser emission in the methanol multi-beam (MMB) Survey (Caswell et al. 2010.) Class II methanol masers are a well-known sign post of massive star forming regions and may be utilized to probe their relatively poorly understood formation. It is possible that these non-detections are simply weak masers that are potentially associated with a younger evolutionary phase of MYSOs as hypothesized by Olmi et al. (2014). The sources were chosen to sample various stages of evolution, having similar 21 to 8 micron flux ratios and bolometric luminosities as other MYSOs with previous class II methanol maser detections. We observed all 4 MYSOs with ATCA (~2" resolution) at 10 times deeper sensitivity than previously obtained with the MMB survey and have a spectral resolution of 0.087kms^-1 . The raw data is reduced using the program Miriad (Sault, R. J., et al., 1995) and deconvolutioned using the program CASA (McMullin, J. P., et al. 2007.) We determine one of the four observed MYSOs is harboring a weak class II methanol maser. We discuss the possibility of sensitivity limitations on the remaining sources as well as environmental and evolutionary differences between the sources.

  1. The T-cell anergy induced by Leishmania amazonensis antigens is related with defective antigen presentation and apoptosis

    Directory of Open Access Journals (Sweden)

    Roberta O. Pinheiro

    2004-09-01

    Full Text Available Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease associated with anergic immune responses. In this study we show that the crude antigen of Leishmania amazonensis (LaAg but not L. braziliensis promastigotes (LbAg contains substances that suppress mitogenic and spontaneous proliferative responses of T cells. The suppressive substances in LaAg are thermoresistant (100ºC/1h and partially dependent on protease activity. T cell anergy was not due to a decreased production of growth factors as it was not reverted by addition of exogenous IL-2, IL-4, IFN-gamma or IL-12. LaAg did not inhibit anti-CD3-induced T cell activation, suggesting that anergy was due to a defect in antigen presentation. It was also not due to cell necrosis, but was accompanied by expressive DNA fragmentation in lymph node cells, indicative of apoptosis. Although pre-incubation of macrophages with LaAg prevented their capacity to present antigens, this effect was not due to apoptosis of the former. These results suggest that the T cell anergy found in diffuse leishmaniasis may be the result of parasite antigen-driven apoptosis of those cells following defective antigen presentation.A Leishmania amazonensis é o principal agente etiológico da leishmaniose cutânea difusa, uma doença associada a respostas imunes anérgicas. Neste estudo nós mostramos que o extrato bruto de promastigotas de Leishmania amazonensis (LaAg, mas não de L. braziliensis (LbAg, contém substâncias que suprimem respostas proliferativas, espontâneas e mitogênicas, de células T. As substâncias supressoras no LaAg são termo-resistentes (100°C/1h e parcialmente dependentes da atividade de proteases. A anergia de células T não foi devida à diminuição na produção de fatores de crescimento, uma vez que não foi revertida pela adição de: IL-2, IL-4, IFN-gama ou IL-12. O LaAg não inibiu a ativação de células T induzida por anti-CD3, sugerindo que a anergia

  2. Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Charles Arama

    Full Text Available The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs, and in particular dendritic cells (DCs are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR

  3. Má oclusão Classe II de Angle tratada sem extrações e com controle de crescimento Angle Class II malocclusion treated without extractions and with growth control

    Directory of Open Access Journals (Sweden)

    Flávia Artese

    2009-06-01

    Full Text Available A má oclusão Classe II de Angle é caracterizada por uma discrepância dentária anteroposterior, que geralmente está acompanhada por alterações esqueléticas. O tratamento ortodôntico precoce permite a correção da discrepância esquelética por controle de crescimento (primeira fase, o que favorece a correção do posicionamento dentário, mais tardiamente (segunda fase. Este relato descreve o tratamento de um caso de má oclusão Classe II, divisão 2, de Angle, em duas fases, e foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO. O caso foi avaliado como representante da Categoria 1, ou seja, má oclusão Classe II de Angle tratada sem extrações dentárias e com controle de crescimento.Angle Class II malocclusion is characterized by an anteroposterior dental discrepancy which is generally accompanied by skeletal disharmonies. Early orthodontic treatment allows the correction of skeletal discrepancies using growth control (first phase which favors later correction of tooth positioning (second phase. This case report describes an Angle Class II, division 2, malocclusion treated in two phases and was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as part of the requirements for BBO certification. It was evaluated as a Category 1 case, i.e., Class II malocclusion treated without extractions, with growth control.

  4. HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations.

    Science.gov (United States)

    Vargas-Alarcón, Gilberto; Granados, Julio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Canto-Cetina, Thelma; Coral-Vázquez, Ramón Mauricio; Areces, Cristina; Gómez-Prieto, Pablo; Arnaiz-Villena, Antonio

    2011-01-01

    We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.

  5. A modified orthodontic protocol for advanced periodontal disease in Class II division 1 malocclusion.

    Science.gov (United States)

    Janson, Marcos; Janson, Guilherme; Murillo-Goizueta, Oscar Edwin Francisco

    2011-04-01

    An interdisciplinary approach is often the best option for achieving a predictable outcome for an adult patient with complex clinical problems. This case report demonstrates the combined periodontal/orthodontic treatment for a 49-year-old woman presenting with a Class II Division 1 malocclusion with moderate maxillary anterior crowding, a 9-mm overjet, and moderate to severe bone loss as the main characteristics of the periodontal disease. The orthodontic treatment included 2 maxillary first premolar extractions through forced extrusion. Active orthodontic treatment was completed in 30 months. The treatment outcomes, including the periodontal condition, were stable 17 months after active orthodontic treatment. The advantages of this interdisciplinary approach are discussed. Periodontally compromised orthodontic patients can be satisfactorily treated, achieving most of the conventional orthodontic goals, if a combined orthodontic/periodontic approach is used.

  6. Tratamento da classe II divisão 1 na dentição mista

    OpenAIRE

    Angelino, André de Brito

    2016-01-01

    Introdução: Os indivíduos portadores da má oclusão de Classe II Divisão 1 possuem diversas etiologias e podem ser encontrados em todas as etnias. As suas características clínicas e radiográficas se agravam com o crescimento e uma vez não tratada, continuam com esta má oclusão por toda sua vida. Para o tratamento ortodôntico na dentição mista recorre-se a dispositivos como aparelhos extra-orais, aparelhos funcionais fixos e removíveis. Objetivo: O objetivo deste trabalho é fazer uma revisão...

  7. Agenesis of maxillary lateral incisor in an Angle Class II, Division 1 malocclusion patient

    Directory of Open Access Journals (Sweden)

    Guilherme Thiesen

    2015-10-01

    Full Text Available The present case report describes the orthodontic treatment of a patient with agenesis of maxillary left lateral incisor and Angle Class II, Division 1 malocclusion. The patient also presented with maxillary midline deviation and inclination of the occlusal plane in the anterior region. Treatment objectives were: correction of sagittal relationship between the maxilla and the mandible; correction of midline deviation, so as to cause maxillary and mandibular midlines to coincide; correction of overbite and leveling of the occlusal plane, so as to create ideal conditions for esthetic rehabilitation of anterior teeth. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as a requirement for the title of certified by the BBO.

  8. Genetic variation in V gene of class II Newcastle disease virus.

    Science.gov (United States)

    Hao, Huafang; Chen, Shengli; Liu, Peng; Ren, Shanhui; Gao, Xiaolong; Wang, Yanping; Wang, Xinglong; Zhang, Shuxia; Yang, Zengqi

    2016-01-01

    The genetic variation and molecular evolution of the V gene of the class II Newcastle disease virus (NDV) isolates with genotypes I-XVIII were determined using bioinformatics. Results indicated that low homology existed in different genotype viruses, whereas high homology often for the same genotypes, exception may be existed within genotypes I, V, VI, and XII. Sequence analysis showed that the genetic variation of V protein was consistent with virus genotype, and specific signatures on the V protein for nine genotypes were identified. Phylogenetic analysis demonstrated that the phylogenetic trees were highly consistent between the V and F genes, with slight discrepancies in the sub-genotypes. Evolutionary rate analyses based on V and F genes revealed the evolution rates varied in genotypes. These data indicate that the genetic variation of V protein is genotype-related and will help in elucidating the molecular evolution of NDV.

  9. Orthodontic camouflage via total arch movement in a Class II with idiopathic condylar resorption

    Directory of Open Access Journals (Sweden)

    Ji-Sung Jang

    2014-01-01

    Full Text Available Idiopathic condylar resorption (ICR, also known as idiopathic condylysis or condylar atrophy, is multifactorial pathology leading to severe mandibular retrognathism. The etiology has been shown to be multifactorial, such as avascular necrosis, traumatic injuries, hormone and autoimmune disease and it is largely difficult to distinguish the exact cause in each individual. In spite of the remarkable morphological alteration, surgical intervention is not readily recruited due to the possibility of recurrence of resorption. In order to restore balanced facial profile and occlusion. In this report, we present a camouflage treatment for skeletal Class II with ICR and facial asymmetry involving total arch movement, for the improvement facial profile and reconstruction of occlusion.

  10. Orthodontic Protocol Using Mini-Implant for Class II Treatment in Patient with Special Needs

    Directory of Open Access Journals (Sweden)

    Fernando Pedrin Carvalho Ferreira

    2016-01-01

    Full Text Available Improving facial and dental appearance and social interaction are the main factors for special needs (SN patients to seek orthodontic treatment. The cooperation of SN patients and their parents is crucial for treatment success. Objective. To show through a case report the satisfactory results, both functional and esthetic, in patients with intellectual disability, congenital nystagmus, and severe scoliosis. Materials Used. Pendulum device with mini-implants as anchorage unit. Results. Improvement of facial and dental esthetics, correction of Class II malocclusion, and no root resorption shown in the radiographic follow-up. Conclusion. Knowing the limitations of SN patients, having a trained team, motivating and counting on the cooperation of parents and patients, and employing quick and low-cost orthodontic therapy have been shown to be the essential factors for treatment success.

  11. Alkali/Surfactant/Polymer Flooding in the Daqing Oilfield Class II Reservoirs Using Associating Polymer

    Directory of Open Access Journals (Sweden)

    Ru-Sen Feng

    2013-01-01

    Full Text Available Hydrophobically modified associating polyacrylamide (HAPAM has good compatibility with the Daqing heavy alkylbenzene sulfonate surfactant. The HAPAM alkali/surfactant/polymer (ASP system can generate ultralow interfacial tension in a wide range of alkali/surfactant concentrations and maintain stable viscosity and interfacial tension for 120 days. The HAPAM ASP system has good injectivity for the Daqing class II reservoirs (100–300 × 10−3 μm2 and can improve oil recovery by more than 25% on top of water flooding. In the presence of both the alkali and the surfactant, the surfactant interacts with the associating groups of the polymer to form more micelles, which can significantly enhance the viscosity of the ASP system. Compared with using HPAM (Mw = 2.5 MDa, using HAPAM can reduce the polymer use by more than 40%.

  12. Prediction of HLA class II alleles using SNPs in an African population.

    Directory of Open Access Journals (Sweden)

    Fasil Tekola Ayele

    Full Text Available Despite the importance of the human leukocyte antigen (HLA gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs. However, the utility of these methods in African populations has not been systematically evaluated.In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1 alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.

  13. Integrated Data Collection Analysis (IDCA) Program - RDX Type II Class 5 Standard, Data Set 1

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorenson, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Moran, Jesse S. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates, Inc., Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Whipple, Richard E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-04-11

    This document describes the results of the first reference sample material—RDX Type II Class 5—examined in the proficiency study for small-scale safety and thermal (SSST) testing of explosive materials for the Integrated Data Collection Analysis (IDCA) Program. The IDCA program is conducting proficiency testing on homemade explosives (HMEs). The reference sample materials are being studied to establish the accuracy of traditional explosives safety testing for each performing laboratory. These results will be used for comparison to results from testing HMEs. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of these materials in perspective with standard military explosives. The results of the study will add SSST testing results for a broad suite of different HMEs to the literature, potentially suggest new guidelines and methods for HME testing, and possibly establish what are the needed accuracies in SSST testing to develop safe handling practices. Described here are the results for impact, friction, electrostatic discharge, and scanning calorimetry analysis of a reference sample of RDX Type II Class 5. The results from each participating testing laboratory are compared using identical test material and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. These results are then compared to historical data from various sources. The performers involved are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Air Force Research Laboratory/ RXQL (AFRL), Indian Head Division, Naval Surface Warfare Center, (IHD-NSWC), and Sandia National Laboratories (SNL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to understand how to compare results when test protocols are not identical.

  14. Microleakage of Class II Combined Amalgam-Composite Restorations Using Different Composites and Bonding Agents

    Directory of Open Access Journals (Sweden)

    F. Sharafeddin

    2008-09-01

    Full Text Available Objective: The purpose of the present study was to assess the microleakage of composite restorations with and without a cervical amalgam base and to compare the results of dif-ferent composites and bonding agents.Materials and Methods: One hundred and twenty mesio-occlusal (MO and disto-occlusal (DO Class II cavities were prepared on sixty extracted permanent premolar teeth. The teeth were randomly divided into four groups of 30 and restored as follows:In group A, the mesio-occlusal cavity (MO, Scotchbond multi purpose plus + Z250 and in the disto-occlusal (DO cavity, Prompt-L-Pop + Z250 were applied. As for group B, in the MO and DO cavities, Clearfil SE Bond + Clearfil APX, and varnish + amalgam (In box + Clearfil SE Bond + Clearfil APX were used respectivelywhile in group C; the teeth were restored with amalgam and varnish mesio-occlusally and with amalgam only disto-occlusally. As for group D, varnish + amalgam (in box + Scotchbond multi purpose plus + Z250 were applied mesio-occlusally and Varnish + Amalgam (in box + Prompt–L–Pop + Z250 disto-occlusally.Marginal leakage was assessed by the degree of dye penetration into various sections of the restored teeth. Chi-square and Fisher's exact tests were used for data analysis.Results: Microleakage in gingival margin was more than that in occlusal margin (P<0.05 and microleakage of combined amalgam-composite restorations was significantly lower than that of conventional composite and amalgam restorations.Conclusion: Marginal microleakage decreased by using amalgam at the base of the box in Class II composite restorations.

  15. Marginal and internal adaptation of class II restorations after immediate or delayed composite placement.

    Science.gov (United States)

    Dietschi, Didier; Monasevic, Manuela; Krejci, Ivo; Davidson, Carel

    2002-01-01

    Direct class II composite restorations still represent a challenge, particularly when proximal limits extend below the CEJ. The aim of this in vitro study was to evaluate the influence of the type of adhesive and the delay between adhesive placement and composite insertion on restoration adaptation. Direct class II MOD box-shaped composite restorations (n=8 per group) were placed on intact human third molars, with proximal margins 1mm above or under CEJ. All cavities were filled with a horizontal layering technique, immediately after adhesive placement (IP) or after a 24h delay (DP). A filled three-component adhesive (OptiBond FL: OB) and a single-bottle, unfilled one (Prime & Bond 2.1: PB) were tested. Marginal adaptation was assessed before and after each phase of mechanical loading (250000 cycles at 50 N, 250000 cycles at 75 N and 500000 cycles at 100 N); internal adaptation was evaluated after test completion. Gold-plated resin replicas were observed in the SEM and restoration quality evaluated in percentages of continuity (C) at the margins and within the internal interface, after sample section. Adaptation to beveled enamel proved satisfactory in all groups. After loading, adaptation to gingival dentin degraded more in PB-IP (C=55.1%) than PB-DP (C=86.9%) or OB-DP (C=89%). More internal defects were observed in PB samples (IP: C=79.2% and DP: C=86.3%) compared to OB samples (IP: C=97.4% and DP: C=98.3%). The filled adhesive (OB) produced a better adaptation than the 'one-bottle' brand (PB), hypothetically by forming a stress-absorbing layer, limiting the development of adhesive failures. Postponing occlusal loading (such as the indirect approach) improved also restoration adaptation.

  16. As implicações da classe II de angle e da desproporção esquelética tipo classe II no aspecto miofuncional The implications of class II angle and class II type skeletal disproportion on the myofunctional aspect

    Directory of Open Access Journals (Sweden)

    Carolina Lisbôa Mezzomo

    2011-08-01

    Full Text Available TEMA: esse trabalho foi baseado na temática de que existe uma associação entre as más oclusões devido a alterações do crescimento craniofacial, e, por conseguinte, a existência de alterações miofuncionais. OBJETIVOS: estudar a associação entre as más oclusões tipo classe II desencadeadas por alterações do crescimento craniofacial e as disfunções do sistema estomatognático (alterações miofuncionais: fala, mastigação, deglutição e fonação. CONCLUSÃO: pode-se concluir que alterações estruturais da face podem ter influência na funcionalidade das mesmas, portanto, enfatiza-se a importância do trabalho multidisciplinar entre os profissionais envolvidos em cada uma dessas aéreas para que o prognóstico desses casos seja pertinente de relevantes melhoras.BACKGROUND: this work has been based on the theme that there is an association between malocclusion due to change in craniofacial growth, and therefore, the existence of malfunctioning abnormalities. PURPOSE: to study the strong association among the malocclusion class II triggered by changes in craniofacial growth and dysfunctions of the stomatognathic system (myofunctional disorders - speech, chewing, swallowing and phonation. CONCLUSION: it may be concluded that structural changes of the face may affect its, and therefore, the importance of multidisciplinary work among professionals involved in each of those areas, is emphasized, so that the prognosis of these cases may have relevant and important improvements.

  17. Stability of Class II treatment with the Bionator followed by fixed appliances

    Directory of Open Access Journals (Sweden)

    Manoela Favaro FRANCISCONI

    2013-12-01

    Full Text Available Objective: This prospective study assessed the stability of Class II treatment with the Bionator, followed by fixed appliances, 10 years after treatment. Material and Methods: The experimental group comprised 23 patients of both sexes (10 boys, 13 girls at a mean initial age of 11.74 years (late mixed or early permanent dentitions, treated for a mean period of 3.55 years who were evaluated at three stages: initial (T1, final (T2 and long-term posttreatment (T3. A total of 69 lateral cephalograms were evaluated and 69 dental casts were measured using the PAR index. The difference between initial and final PAR indexes, the percentage of occlusal improvement obtained with therapy and the percentage of relapse were calculated, using the PAR index. The variables were compared by repeated measures analysis of variance (ANOVA followed by Tukey tests. Results: The significant improvement in apical base relationship, the palatal inclination of the maxillary incisors and the labial inclination of the mandibular incisors, and the significant improvement in molar relationship and reduction of overjet and overbite, obtained with treatment, remained stable in the long-term posttreatment period. There was also significant improvement in the occlusal relationships which remained stable in the long-term posttreatment period. The percentage of occlusal improvement obtained was of 81.78% and the percentage of relapse was of 4.90%. Conclusions: Treatment of Class II division 1 malocclusions with the Bionator associated with fixed appliances showed to be stable in the long-term posttreatment period.

  18. Influence of different restorative techniques on marginal seal of class II composite restorations

    Directory of Open Access Journals (Sweden)

    Sinval Adalberto Rodrigues Junior

    2010-02-01

    Full Text Available OBJECTIVE: To evaluate the gingival marginal seal in class II composite restorations using different restorative techniques. MATERIAL AND METHODS: Class II box cavities were prepared in both proximal faces of 32 sound human third molars with gingival margins located in either enamel or dentin/cementum. Restorations were performed as follows: G1 (control: composite, conventional light curing technique; G2: composite, soft-start technique; G3: amalgam/composite association (amalcomp; and G4: resin-modified glass ionomer cement/composite, open sandwich technique. The restored specimens were thermocycled. Epoxy resin replicas were made and coated for scanning electron microscopy examination. For microleakage evaluation, teeth were coated with nail polish and immersed in dye solution. Teeth were cut in 3 slices and dye penetration was recorded (mm, digitized and analyzed with Image Tool software. Microleakage data were analyzed statistically by non-parametric Kruskal-Wallis and Mann-Whitney tests. RESULTS: Leakage in enamel was lower than in dentin (p<0.001. G2 exhibited the lowest leakage values (p<0.05 in enamel margins, with no differences between the other groups. In dentin margins, groups G1 and G2 had similar behavior and both showed less leakage (p<0.05 than groups G3 and G4. SEM micrographs revealed different marginal adaptation patterns for the different techniques and for the different substrates. CONCLUSION: The soft-start technique showed no leakage in enamel margins and produced similar values to those of the conventional (control technique for dentin margins.

  19. New susceptibility variants to narcolepsy identified in HLA class II region.

    Science.gov (United States)

    Miyagawa, Taku; Toyoda, Hiromi; Hirataka, Akane; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Imai, Makoto; Fujimura, Yota; Tamura, Yoshiyuki; Ikegami, Azusa; Wada, Yamato; Moriya, Shunpei; Furuya, Hirokazu; Kato, Mitsuhiro; Omata, Naoto; Kojima, Hiroto; Kashiwase, Koichi; Saji, Hiroh; Khor, Seik-Soon; Yamasaki, Maria; Wada, Yuji; Ishigooka, Jun; Kuroda, Kenji; Kume, Kazuhiko; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Hirata, Koichi; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-02-01

    Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

  20. A Randomized 10-year Prospective Follow-up of Class II Nanohybrid and Conventional Hybrid Resin Composite Restorations

    DEFF Research Database (Denmark)

    van Dijken, Jan Wv; Pallesen, Ulla

    2014-01-01

    Purpose: To evaluate the 10-year durability of a nanohybrid resin composite in Class II restorations in a randomized controlled intraindividual comparison with its conventional hybrid resin composite predecessor. Materials and Methods: Each of 52 participants received at least two Class II...... restorations that were as similar as possible. The cavities were chosen at random to be restored with a nanohybrid resin composite (Excite/Tetric EvoCeram (TEC); n = 61) and a conventional hybrid (Excite/Tetric Ceram (TC); n = 61). The restorations were evaluated with slightly modified USPHS criteria...... investigated resin composites. Conclusion: The nanohybrid and the conventional hybrid resin composite showed good clinical effectiveness in extensive Class II restorations during the 10-year study....

  1. Klammt open elastic activator and twin blocks in Class II malocclusion treatment.

    Directory of Open Access Journals (Sweden)

    Eduardo Maikel Curbeira Hernández

    2009-04-01

    Full Text Available Background: Klammt open elastic activator and twin blocks have been two of the most worldwide studied functional appliances; however, there are different opinions about their effect on the cranium-facial complex. Objective: To determine the efficacy of these appliances in the functional treatment in Class II division I syndrome in early mixed teething. Methods: Prospective, cuasi experimental, “before-after” study without control group, including all children between 6 and 9 years of Area II in Cienfuegos municipality. After applying inclusion criteria, 20 patients were selected through simple randomized sampling and distributed in two groups, one for each technique. Lateral cranium teleradiographies were taken at the beginning and after a year of treatment, and lineal and/or angular measurements of Steiner, Ricketts, McNamara and Legan Burstone cephalograms were applied. Results: Favourable changes in cranium lateral radiographies measurements were obtained mainly from therapy with twin blocks. There was a decrease in the angle formed by the joint planes nasion-point A and nasion-point B and facial convexity, increase in mandible length and inferior facial height. Nasolabial angle and labial protuberance didn´t increase significantly. Conclusions: treated patients positively modified their bio-typology, and growth trend showed positive variations during functional therapy.

  2. N-containing Ag(I) and Hg(II) complexes: a new class of antibiotics.

    Science.gov (United States)

    Sabounchei, Seyyed Javad; Shahriary, Parisa

    2013-01-01

    Several classes of antimicrobial compounds are presently available; microorganism's resistance to these drugs constantly emerges. In order to prevent this serious medical problem, the elaboration of new types of antibacterial agents or the expansion of bioactivity of the naturally known biosensitive compounds is a very interesting research problem. The synthesis and characterization of metal complexes with organic bioactive ligands is one of the promising fields for the search. The biological activities of the metal complexes differ from those of either the ligand or the metal ion. The results obtained thus far have led to the conclusion that structural factors, which govern antimicrobial activities, are strongly dependent on the central metal ion. A review of papers dealing with the Ag(I) and Hg(II) complexes of N donor ligands is presented. These metal complexes of N-chelating ligands have attracted considerable attention because of their interesting physicochemical properties and pronounced biological activities. This review will mainly focus on the preparation procedures and antibacterial properties of free organic ligands and the corresponding complexes. Finally, a research about antimicrobial properties of new Hg(II) complexes with 5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione (L) and various halogen ions, HgL2X2 (X = Cl¯ (49), Br¯ (50), and I¯ (51)), is reported. Noteworthy antimicrobial activities, evaluated by minimum inhibitory concentration, for these complexes were observed.

  3. Characterization and evolution of MHC class II B genes in Galápagos marine iguanas (Amblyrhynchus cristatus).

    Science.gov (United States)

    Glaberman, Scott; Moreno, Maria A; Caccone, Adalgisa

    2009-08-01

    Major histocompatibility complex (MHC) class II molecules play a key role in the adaptive immune system of vertebrates. Class II B genes appear to evolve in a very different manner in mammals and birds. Orthology is commonly observed among mammal loci, while genes tend to cluster phylogenetically within bird species. Here we present class II B data from a representative of another major group of amniotes, the squamates (i.e. lizards, snakes, amphisbaenians), with the ultimate goal of placing mammalian and avian MHC evolution into a broader context. In this study, eight class II B cDNA sequences were obtained from the Galápagos marine iguana (Amblyrhynchus cristatus) which were divided into five locus groups, Amcr-DAB1 through -DAB5, based on similarities along most of the coding and noncoding portions of the transcribed gene. All marine iguana sequences were monophyletic with respect to class II genes from other vertebrates indicating that they originated from a common ancestral locus after squamates split from other reptiles. The beta-1 domain, which is involved in antigen binding, exhibited signatures of positive selection as well as interlocus gene conversion in both long and short tracts-a pattern also observed in birds and fish, but not in mammals. On the other hand, the beta-2 domain was divergent between gene groups, which is characteristic of mammals. Based on these results, we preliminarily show that squamate class II B genes have been shaped by a unique blend of evolutionary forces that have been observed in differing degrees in other vertebrates.

  4. Long maximal incremental tests accurately assess aerobic fitness in class II and III obese men.

    Science.gov (United States)

    Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Capodaglio, Paolo; Brunani, Amelia; Fanari, Paolo; Salvadori, Alberto; Malatesta, Davide

    2015-01-01

    This study aimed to compare two different maximal incremental tests with different time durations [a maximal incremental ramp test with a short time duration (8-12 min) (STest) and a maximal incremental test with a longer time duration (20-25 min) (LTest)] to investigate whether an LTest accurately assesses aerobic fitness in class II and III obese men. Twenty obese men (BMI≥35 kg.m-2) without secondary pathologies (mean±SE; 36.7±1.9 yr; 41.8±0.7 kg*m-2) completed an STest (warm-up: 40 W; increment: 20 W*min-1) and an LTest [warm-up: 20% of the peak power output (PPO) reached during the STest; increment: 10% PPO every 5 min until 70% PPO was reached or until the respiratory exchange ratio reached 1.0, followed by 15 W.min-1 until exhaustion] on a cycle-ergometer to assess the peak oxygen uptake [Formula: see text] and peak heart rate (HRpeak) of each test. There were no significant differences in [Formula: see text] (STest: 3.1±0.1 L*min-1; LTest: 3.0±0.1 L*min-1) and HRpeak (STest: 174±4 bpm; LTest: 173±4 bpm) between the two tests. Bland-Altman plot analyses showed good agreement and Pearson product-moment and intra-class correlation coefficients showed a strong correlation between [Formula: see text] (r=0.81 for both; p≤0.001) and HRpeak (r=0.95 for both; p≤0.001) during both tests. [Formula: see text] and HRpeak assessments were not compromised by test duration in class II and III obese men. Therefore, we suggest that the LTest is a feasible test that accurately assesses aerobic fitness and may allow for the exercise intensity prescription and individualization that will lead to improved therapeutic approaches in treating obesity and severe obesity.

  5. Long maximal incremental tests accurately assess aerobic fitness in class II and III obese men.

    Directory of Open Access Journals (Sweden)

    Stefano Lanzi

    Full Text Available This study aimed to compare two different maximal incremental tests with different time durations [a maximal incremental ramp test with a short time duration (8-12 min (STest and a maximal incremental test with a longer time duration (20-25 min (LTest] to investigate whether an LTest accurately assesses aerobic fitness in class II and III obese men. Twenty obese men (BMI≥35 kg.m-2 without secondary pathologies (mean±SE; 36.7±1.9 yr; 41.8±0.7 kg*m-2 completed an STest (warm-up: 40 W; increment: 20 W*min-1 and an LTest [warm-up: 20% of the peak power output (PPO reached during the STest; increment: 10% PPO every 5 min until 70% PPO was reached or until the respiratory exchange ratio reached 1.0, followed by 15 W.min-1 until exhaustion] on a cycle-ergometer to assess the peak oxygen uptake [Formula: see text] and peak heart rate (HRpeak of each test. There were no significant differences in [Formula: see text] (STest: 3.1±0.1 L*min-1; LTest: 3.0±0.1 L*min-1 and HRpeak (STest: 174±4 bpm; LTest: 173±4 bpm between the two tests. Bland-Altman plot analyses showed good agreement and Pearson product-moment and intra-class correlation coefficients showed a strong correlation between [Formula: see text] (r=0.81 for both; p≤0.001 and HRpeak (r=0.95 for both; p≤0.001 during both tests. [Formula: see text] and HRpeak assessments were not compromised by test duration in class II and III obese men. Therefore, we suggest that the LTest is a feasible test that accurately assesses aerobic fitness and may allow for the exercise intensity prescription and individualization that will lead to improved therapeutic approaches in treating obesity and severe obesity.

  6. T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides

    DEFF Research Database (Denmark)

    Larsen, S L; Pedersen, L O; Buus, S;

    1996-01-01

    the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing. The NH2-terminal end of the longer peptide could, even while bound to major histocompatibility complex (MHC) class II molecules, be digested by APN with dramatic consequences for T cell...... antigen recognition. This could be demonstrated both in cell-free systems using purified reagents and in cellular systems. Thus, MHC class II and APN may act in concert to generate the final T cell epitopes....

  7. Subcellular localization of class II HDAs in Arabidopsis thaliana: nucleocytoplasmic shuttling of HDA15 is driven by light.

    Directory of Open Access Journals (Sweden)

    Malona V Alinsug

    Full Text Available Class II histone deacetylases in humans and other model organisms undergo nucleocytoplasmic shuttling. This unique functional regulatory mechanism has been well elucidated in eukaryotic organisms except in plant systems. In this study, we have paved the baseline evidence for the cytoplasmic and nuclear localization of Class II HDAs as well as their mRNA expression patterns. RT-PCR analysis on the different vegetative parts and developmental stages reveal that Class II HDAs are ubiquitously expressed in all tissues with minimal developmental specificity. Moreover, stable and transient expression assays using HDA-YFP/GFP fusion constructs indicate cytoplasmic localization of HDA5, HDA8, and HDA14 further suggesting their potential for nuclear transport and deacetylating organellar and cytoplasmic proteins. Organelle markers and stains confirm HDA14 to abound in the mitochondria and chloroplasts while HDA5 localizes in the ER. HDA15, on the other hand, shuttles in and out of the nucleus upon light exposure. In the absence of light, it is exported out of the nucleus where further re-exposition to light treatments signals its nuclear import. Unlike HDA5 which binds with 14-3-3 proteins, HDA15 fails to interact with these chaperones. Instead, HDA15 relies on its own nuclear localization and export signals to navigate its subcellular compartmentalization classifying it as a Class IIb HDA. Our study indicates that nucleocytoplasmic shuttling is indeed a hallmark for all eukaryotic Class II histone deacetylases.

  8. Distalization of maxillary arch and correction of Class II with mini-implants: A report of two cases

    Directory of Open Access Journals (Sweden)

    Pawankumar Dnyandeo Tekale

    2015-01-01

    Full Text Available This article reports the successful use of mini-screws in the maxilla to treat two patients of age 21-year and 17-year-old girls. Both the patients had a skeletal Class II malocclusion with protrusive maxillary teeth and angels Class II mal-occlusion. Temporary anchorage devices (TADs in the posterior dental region between maxillary second premolar and maxillary first molar teeth on both sides were used as anchorage for the retraction and intrusion of her maxillary anterior teeth. Those appliances, combined with a compensatory curved maxillary archwire, eliminated spacing, deep bite, forwardly placed and proclined upper front teeth and the protrusive profile, corrected the molar relationship from Class II to Class I. With no extra TADs in the anterior region for intrusion, the treatment was workable and simple. The patient received a satisfactory occlusion and an attractive smile. This technique requires minimal compliance and is particularly useful for correcting Class II patients with protrusive maxillary front teeth and dental deep bite.

  9. Subcellular localization of class II HDAs in Arabidopsis thaliana: nucleocytoplasmic shuttling of HDA15 is driven by light.

    Science.gov (United States)

    Alinsug, Malona V; Chen, Fang Fang; Luo, Ming; Tai, Ready; Jiang, Liwen; Wu, Keqiang

    2012-01-01

    Class II histone deacetylases in humans and other model organisms undergo nucleocytoplasmic shuttling. This unique functional regulatory mechanism has been well elucidated in eukaryotic organisms except in plant systems. In this study, we have paved the baseline evidence for the cytoplasmic and nuclear localization of Class II HDAs as well as their mRNA expression patterns. RT-PCR analysis on the different vegetative parts and developmental stages reveal that Class II HDAs are ubiquitously expressed in all tissues with minimal developmental specificity. Moreover, stable and transient expression assays using HDA-YFP/GFP fusion constructs indicate cytoplasmic localization of HDA5, HDA8, and HDA14 further suggesting their potential for nuclear transport and deacetylating organellar and cytoplasmic proteins. Organelle markers and stains confirm HDA14 to abound in the mitochondria and chloroplasts while HDA5 localizes in the ER. HDA15, on the other hand, shuttles in and out of the nucleus upon light exposure. In the absence of light, it is exported out of the nucleus where further re-exposition to light treatments signals its nuclear import. Unlike HDA5 which binds with 14-3-3 proteins, HDA15 fails to interact with these chaperones. Instead, HDA15 relies on its own nuclear localization and export signals to navigate its subcellular compartmentalization classifying it as a Class IIb HDA. Our study indicates that nucleocytoplasmic shuttling is indeed a hallmark for all eukaryotic Class II histone deacetylases.

  10. Aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during West Nile virus infection.

    Directory of Open Access Journals (Sweden)

    Bradley S Schneider

    Full Text Available West Nile virus (WNV is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-beta and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively, whilst transiently enhancing interleukin-10 (IL-10 expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively in the skin and draining lymph nodes. These results suggest that mosquito

  11. Treatment of class II and class III maloccolusion by using churro jumper: an efficient, inexpensive and uncomplicated fixed flexible functional technique

    OpenAIRE

    Mani, Shubhangi Amit; Mote, Nilesh; Pawar, Kunal Dilip; Mishra, Prashantkumar; Mishra, Richa Anil; Rai, Rajlaxmi Rajaram

    2016-01-01

    Functional orthopedic treatment seeks to improve skeletal and dental relationship of the jaws. The challenging task is to correctly position jaws antero-posteriorly and vertically with correct overbite, overjet and Centric relation. The Churro Jumper is an efficient, inexpensive and uncomplicated fixed flexible functional appliance. It is used to evaluate the efficacy of the Churro Jumper appliance in treatment of skeletal Class II malocclusion with retrognathic mandible. Churro Jumper contri...

  12. HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

    Science.gov (United States)

    Lou, H; Li, H C; Kuwayama, M; Yashiki, S; Fujiyoshi, T; Suehara, M; Osame, M; Yamashita, M; Hayami, M; Gurtsevich, V; Ballas, M; Imanishi, T; Sonoda, S

    1998-11-01

    The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

  13. Uso do aparelho de Thurow no tratamento da má oclusão esquelética de Classe II The use of Thurow's appliance in the treatment of skeletal class II malocclusion

    Directory of Open Access Journals (Sweden)

    Maíra Massuia de Souza

    2005-08-01

    Full Text Available O objetivo deste trabalho foi realizar uma revisão de literatura em relação ao tratamento da má oclusão esquelética de Classe II com a utilização do splint maxilar removível associado à tração alta, realçando sua influência no crescimento ósseo e seus benefícios. Através do relato do caso clínico será mostrada a confecção e os efeitos do aparelho de Thurow quando utilizado no período da dentadura mista, para a correção da Classe II esqueléticaThe aim of this study was to review the literature concerning the treatment of Class II malocclusion with removable maxillary splint associated to the high traction, enhancing its influence in the bony growth and its benefits. This clinical case will show the fabrication and the effects of Thurow's appliance, when it's used in the mixed dentition for the correction skeletal class II malocclusion.

  14. HLA class I and class II conserved extended haplotypes and their fragments or blocks in Mexicans: implications for the study of genetic diversity in admixed populations.

    Directory of Open Access Journals (Sweden)

    Joaquín Zúñiga

    Full Text Available Major histocompatibility complex (MHC genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C, and class II (HLA-DRB1, -DQB1 genes using high-resolution sequence based typing (SBT method and we structured the blocks and conserved extended haplotypes (CEHs in 234 non-related admixed Mexican individuals (468 haplotypes by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs and HLA-B that correlated with the frequency of most probable ancestral HLA-C/-B and -DRB1/-DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations.

  15. Marginal sealing ability of silorane and methacrylate resin composites in class II cavities: A scanning electron microscopic study

    Directory of Open Access Journals (Sweden)

    Jyothi Kashi Nanjundasetty

    2013-01-01

    Intergroup comparison of subgroup A did not show statistically significant difference, whereas subgroup B showed statistically significant difference for microleakage between group I and group II (P = 0.003, group III and group II (P = 0.002. Conclusion: Silorane resin composite and methacrylate resin with liner showed significantly less microleakage in class II cavities along the gingival margin placed below CEJ compared to methacrylate resin without liner. All the study groups showed less microleakage and microgap formation along the gingival margin placed above CEJ.

  16. Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity

    DEFF Research Database (Denmark)

    Merelo, Paz; Ram, Hathi; Caggiano, Monica Pia

    2016-01-01

    A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD-...

  17. Development of a simultaneous high resolution typing method for three SLA class II genes, SLA-DQA, SLA-DQB1, and SLA-DRB1 and the analysis of SLA class II haplotypes.

    Science.gov (United States)

    Le, MinhThong; Choi, Hojun; Choi, Min-Kyeung; Cho, Hyesun; Kim, Jin-Hoi; Seo, Han Geuk; Cha, Se-Yeon; Seo, Kunho; Dadi, Hailu; Park, Chankyu

    2015-06-15

    The characterization of the genetic variations of major histocompatibility complex (MHC) is essential to understand the relationship between the genetic diversity of MHC molecules and disease resistance and susceptibility in adaptive immunity. We previously reported the development of high-resolution individual locus typing methods for three of the most polymorphic swine leukocyte antigens (SLA) class II loci, namely, SLA-DQA, SLA-DQB1, and SLA-DRB1. In this study, we extensively modified our previous protocols and developed a method for the simultaneous amplification of the three SLA class II genes and subsequent analysis of individual loci using direct sequencing. The unbiased and simultaneous amplification of alleles from the all three hyper-polymorphic and pseudogene containing genes such as MHC genes is extremely challenging. However, using this method, we demonstrated the successful typing of SLA-DQA, SLA-DQB1, and SLA-DRB1 for 31 selected individuals comprising 26 different SLA class II haplotypes which were identified from 700 animals using the single locus typing methods. The results were identical to the known genotypes from the individual locus typing. The new method has significant benefits over the individual locus typing, including lower typing cost, use of less biomaterial, less effort and fewer errors in handling large samples for multiple loci. We also extensively characterized the haplotypes of SLA class II genes and reported three new haplotypes. Our results should serve as a basis to investigate the possible association between polymorphisms of MHC class II and differences in immune responses to exogenous antigens.

  18. Artificial antigen-presenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8+CD28+ T lymphocyte responses

    Institute of Scientific and Technical Information of China (English)

    Xia Yu; Yuan Fang; Xi Li; Nuo Zhou; Yong-Xiang Zhao; Xiao-Ling Lu; Jian He; Sodaly Mongkhoune; Yi Peng; Yuan Xie; Jing Su; Su-Fang Zhou; Xiao-Xun Xie; Guo-Rong Luo

    2013-01-01

    To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8+CD28+ cytotoxic T lymphocyte (CTL) responses. Methods: Cell-sized Dynabeads® M-450 Epoxy beads coated with H-2Kb:Ig-TRP2180-188 and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8+CD28+CTL responses with the help of IL-21 and IL-15. Dimer staining, proliferation, ELISPOT, and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs. Results: Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8+CD28+ CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN-γ under the stimulation of H-2Kb:Ig-TRP2-aAPCs, IL-15, and IL-21. In addition, cytotoxicity experiments showed that induced CTLs have specific killing activity of target cells. Conclusions: The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8+CD28+ CTLs against the melanoma. Our study provides evidence for a novel adoptive immunotherapy against tumors.

  19. 1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells.

    NARCIS (Netherlands)

    Khoo, A.L.; Joosten, I.; Michels, M.; Woestenenk, R.M.; Preijers, F.W.M.B.; He, X.; Netea, M.G.; Ven, A.J.A.M. van der; Koenen, H.J.P.M.

    2011-01-01

    Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen-presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] can directly affect the proliferation and functio

  20. MHC class II up-regulation and co-localization with Fas in experimental models of immune-mediated bone marrow failure

    Science.gov (United States)

    Erie, Andrew J.; Samsel, Leigh; Takaku, Tomoiku; Desierto, Marie J.; Keyvanfar, Keyvan; McCoy, J. Philip; Young, Neal S.; Chen, Jichun

    2011-01-01

    Objective To test the hypothesis that gamma interferon (IFN-γ) promotes MHC class II expression on bone marrow (BM) cell targets that facilitates T cell-mediated BM destruction in immune-mediated BM failure. Materials and Methods Allogeneic lymph node (LN) cells were infused into MHC or minor histocompatibility antigen (minor-H) mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas co-localization was detected by ImageStream Imaging Flow Cytometry and other cell-cell associations were visualized by confocal microscopy. T cell-mediated BM cell apoptosis and effects of IFN-γ on MHC class II-Fas co-localization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry. Results BM failure animals had significantly up-regulated MHC class II expression on CD4−CD8−CD11b−CD45R− residual BM cells and significantly increased MHC class II-Fas co-localization on BM CD150+ and CD34+ hematopoietic cells. MHC class II+Fas+ BM cells were closely associated with CD4+ T cells in the BM of affected animals, and they were significantly more responsive to T-cell mediated cell apoptosis relative to MHC class II−Fas− BM cells. Infusion of IFN-γ-deficient LN cells into minor-H mismatched recipients resulted in no MHC class II-Fas up-regulation and no clinically overt BM failure. Treatment with recombinant IFN-γ significantly increased both MHC class II-Fas co-expression and co-localization on normal BM cells. Conclusion Elevation of the inflammatory cytokine IFN-γ stimulated MHC class II expression and MHC class II-Fas co-localization, which may facilitate T-cell mediated cell destruction. PMID:21635935

  1. Marginal Integrity of Bulk Versus Incremental Fill Class II Composite Restorations.

    Science.gov (United States)

    Al-Harbi, F; Kaisarly, D; Bader, D; El Gezawi, M

    2016-01-01

    Bulk-fill composites have been introduced to facilitate the placement of deep direct resin composite restorations. This study aimed at analyzing the cervical marginal integrity of bulk-fill vs incremental and open-sandwich class II resin composite restorations after thermomechanical cycling using replica scanning electron microscopy (SEM) and ranking according to the World Dental Federation (FDI) criteria. Box-only class II cavities were prepared in 91 maxillary premolars with the gingival margin placed 1 mm above and below the cemento-enamel junction. Eighty-four premolars were divided into self-etch and total-etch groups, then subdivided into six restorative subgroups (n=7): 1-Tetric Ceram HB (TC) was used incrementally and in the open-sandwich technique with 2-Tetric EvoFlow (EF) and 3-Smart Dentin Replacement (SD). Bulk-fill restoratives were 4-SonicFill (SF), 5-Tetric N-Ceram Bulk Fill (TN), and 6-Tetric EvoCeram Bulk Fill (TE). In subgroups 1-5, Tetric N-Bond self-etch and Tetric N-Bond total-etch adhesives were used, whereas in subgroup 6, AdheSE self-etch and ExciTE F total etch were used. One more group (n=7) was restored with Filtek P90 Low Shrink Posterior Restorative (P9) only in combination with its self-etch P90 System Adhesive. Materials were manipulated and light cured (20 seconds, 1600 mW/cm(2)), and restorations were artificially aged by thermo-occlusal load cycling. Polyvinyl-siloxane impressions were taken and poured with epoxy resin. Resin replicas were examined by SEM (200×) for marginal sealing, and percentages of perfect margins were analyzed. Moreover, samples were examined using loupes (3.5×) and explorers and categorized according to the FDI criteria. Results were statistically analyzed (SEM by Kruskal-Wallis test and FDI by chi-square test) without significant differences in either the replica SEM groups (p=0.848) or the FDI criteria groups (p>0.05). The best SEM results at the enamel margin were in TC+EF/total-etch and SF

  2. Changes in soft tissue profile using functional appliances in the treatment of skeletal class II malocclusion

    Directory of Open Access Journals (Sweden)

    Stamenković Zorana

    2015-01-01

    Full Text Available Introduction. The effects of orthodontic treatment are considered to be successful if the facial harmony is achieved, while the structures of soft tissue profile are in harmony with skeletal structures of neurocranium and viscerocranium. In patients with skeletal distal bite caused by mandibular retrognathism, facial esthetics is disturbed often, in terms of pronounced convexity of the profile and change in the position and relationship of the lips. Objective. The aim of this study was to determine the extent of soft tissue profile changes in patients with skeletal Class II malocclusion treated with three different orthodontic appliances: Fränkel functional regulator type I (FR-I, Balters’ Bionator type I and Hotz appliance. Methods. The study included 60 patients diagnosed with skeletal Class II malocclusion caused by mandibular retrognathism, in the period of early mixed dentition. Each subgroup of 20 patients was treated with a variety of orthodontic appliances. On the lateral cephalogram, before and after treatment, the following parameters were analyzed: T angle, H angle, the height of the upper lip, the position of the upper and lower lip in relation to the esthetic line. Within the statistical analysis the mean, maximum, minimum, standard deviation, coefficient of variation, two-factor analysis of variance with repeated measures and the factor analysis of variance were calculated using ANOVA, Bonferroni test and Student’s t-test. Results. A significant decrease of angles T and H was noticed in the application of FR-I, from 21.60° to 17.15°, and from 16.45° to 13.40° (p<0.001. FR-I decreased the height of the upper lip from 26.15 mm to 25.85 mm, while Hotz appliance and Balters’ Bionator type I increased the height of the upper lip, thereby deteriorating esthetics of the patient. Conclusion. All used orthodontic appliances lead to changes in soft tissue profile in terms of improving facial esthetics, with the most distinctive

  3. Trans-species polymorphism and selection in the MHC class II DRA genes of domestic sheep.

    Directory of Open Access Journals (Sweden)

    Keith T Ballingall

    Full Text Available Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries. We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201 differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901, which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T

  4. Major histocompatibility (MH) class II ß gene polymorphism influences disease resistance of common carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Rakus, K.L.; Wiegertjes, G.F.; Jurecka, P.M.; Walker, P.D.; Pilarczyk, A.; Irnazarow, I.

    2009-01-01

    Genes of the major histocompatibility complex (MHC) are crucial elements of adaptive immunity. High polymorphism renders the MHC genes highly suitable for studies on association with disease resistance. In common carp (Cyprinus carpio L.), there are two paralogous groups of MH class II B genes, Cyca

  5. 40 CFR 147.903 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.903 Section 147.903 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  6. 40 CFR 147.1154 - Existing Class II enhanced recovery and hydrocarbon storage wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... and hydrocarbon storage wells authorized by rule. 147.1154 Section 147.1154 Protection of Environment... UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1154 Existing Class II enhanced recovery and hydrocarbon... determines that the owner or operator of an existing enhanced recovery or hydrocarbon storage will may not...

  7. 40 CFR 147.303 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.303 Section 147.303 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  8. 40 CFR 147.253 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.253 Section 147.253 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  9. T cells induce extended class II MHC compartments in dendritic cells in a Toll-like receptor-dependent manner.

    Science.gov (United States)

    Boes, Marianne; Bertho, Nicolas; Cerny, Jan; Op den Brouw, Marjolein; Kirchhausen, Tomas; Ploegh, Hidde

    2003-10-15

    Interaction of Ag-loaded dendritic cells with Ag-specific CD4 T cells induces the formation of long tubular class II MHC-positive compartments that polarize toward the T cell. We show involvement of a Toll-like receptor-mediated signal in this unusual form of intracellular class II MHC trafficking. First, wild-type dendritic cells loaded with LPS-free Ag failed to show formation of class II-positive tubules upon Ag-specific T cell engagement, but did so upon supplementation of the Ag with low concentrations of LPS. Second, Ag-loaded myeloid differentiation factor 88 -deficient dendritic cells failed to form these tubules upon interaction with T cells, regardless of the presence of LPS. Finally, inclusion of a cell-permeable peptide that blocks TNFR-associated factor 6 function, downstream of myeloid differentiation factor 88, blocked T cell-dependent tubulation. A Toll-like receptor-dependent signal is thus required to allow Ag-loaded dendritic cells to respond to T cell contact by formation of extended endosomal compartments. This activation does not result in massive translocation of class II MHC molecules to the cell surface.

  10. Orthopedic coordination of dentofacial development in skeletal Class II malocclusion in conjunction with edgewise therapy. Part I.

    Science.gov (United States)

    Bass, N M

    1983-11-01

    The skeletal Class II malocclusion may be considered to develop as a failure of the coordinating process to maintain harmonious relationships within the developing dentofacial apparatus. If the skeletal elements are too far apart for adaptation to occur and/or if there are functional abnormalities of the orofacial musculature which inhibit coordination from taking place, a malocclusion will result. An orthopedic technique and appliance system has been developed with the intention of improving those factors responsible for the development and perpetuation of the skeletal Class II malocclusion in a primary stage of treatment. This is accomplished by means of restraint and redirection of forward maxillary growth and an increase in the velocity of mandibular growth. Concurrently, adverse soft-tissue influences are eliminated or ameliorated. Edgewise appliance therapy is subsequently carried out for the final correction. The subject is considered in two articles. This first article describes the effects of the restraint of maxillary growth on craniofacial development and the dental changes produced by a maxillary removable splint with extraoral traction and shows how they can be used clinically for correction of the skeletal Class II malocclusion. The experimental and clinical evidence supporting this approach is considered, and case histories show the clinical use of the maxillary splint. This form of maxillary therapy for the skeletal Class II malocclusion has limitations, and it is desirable for it to be incorporated into a comprehensive orthopedic system.

  11. Twenty -year post-treatment assessment of class II division 1 malocclusion treated with non-extraction approach

    Directory of Open Access Journals (Sweden)

    Ashok Karad

    2013-01-01

    This article describes twenty-year post-treatment assessment of a class II division 1 malocclusion case, treated in the late mixed dentition stage, with the non-extraction treatment approach - molar-inserted headgear along with a fixed appliance therapy.

  12. Extraction of maxillary first molars improves second and third molar inclinations in Class II Division 1 malocclusion

    NARCIS (Netherlands)

    Livas, C.; Halazonetis, D.J.; Booij, J.W.; Katsaros, C.

    2011-01-01

    INTRODUCTION: The aim of this study was to assess the changes in inclination of the maxillary second (M2) and third (M3) molars after orthodontic treatment of Class II Division 1 malocclusion with extraction of maxillary first molars. METHODS: Two groups of subjects were studied. The experimental gr

  13. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency

    Directory of Open Access Journals (Sweden)

    Djidjik Réda

    2012-08-01

    Full Text Available Abstract Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26. Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

  14. Two-year evaluation of the atraumatic restorative treatment approach in primary molars class I and II restorations

    NARCIS (Netherlands)

    da Franca, C.; Colares, V.; van Amerongen, E.

    2011-01-01

    Background.  Atraumatic restorative treatment (ART) has the advantages of reducing pain and fear and of being more cost-effective than the traditional approach. Aim.  The aim of this study was to investigate the survival of ART class I and II restorations in primary molars at 2 years. Design.  The s

  15. 40 CFR 147.1653 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized by rule. 147.1653 Section 147.1653 Protection of... recovery and hydrocarbon storage) and III wells authorized by rule. Maximum injection pressure. The...

  16. 40 CFR 147.503 - Existing Class II (except enhanced recovery and hydrocarbon storage) wells authorized by rule.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Existing Class II (except enhanced recovery and hydrocarbon storage) wells authorized by rule. 147.503 Section 147.503 Protection of... recovery and hydrocarbon storage) wells authorized by rule. Maximum injection pressure. To meet...

  17. 40 CFR 147.1953 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells authorized...

    Science.gov (United States)

    2010-07-01<