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Sample records for cellular hla class

  1. Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides.

    Science.gov (United States)

    Kessler, Jan H; Mommaas, Bregje; Mutis, Tuna; Huijbers, Ivo; Vissers, Debby; Benckhuijsen, Willemien E; Schreuder, Geziena M Th; Offringa, Rienk; Goulmy, Els; Melief, Cornelis J M; van der Burg, Sjoerd H; Drijfhout, Jan W

    2003-02-01

    We report the development, validation, and application of competition-based peptide binding assays for 13 prevalent human leukocyte antigen (HLA) class I alleles. The assays are based on peptide binding to HLA molecules on living cells carrying the particular allele. Competition for binding between the test peptide of interest and a fluorescein-labeled HLA class I binding peptide is used as read out. The use of cell membrane-bound HLA class I molecules circumvents the need for laborious biochemical purification of these molecules in soluble form. Previously, we have applied this principle for HLA-A2 and HLA-A3. We now describe the assays for HLA-A1, HLA-A11, HLA-A24, HLA-A68, HLA-B7, HLA-B8, HLA-B14, HLA-B35, HLA-B60, HLA-B61, and HLA-B62. Together with HLA-A2 and HLA-A3, these alleles cover more than 95% of the Caucasian population. Several allele-specific parameters were determined for each assay. Using these assays, we identified novel HLA class I high-affinity binding peptides from HIVpol, p53, PRAME, and minor histocompatibility antigen HA-1. Thus these convenient and accurate peptide-binding assays will be useful for the identification of putative cytotoxic T lymphocyte epitopes presented on a diverse array of HLA class I molecules. PMID:12559627

  2. Class II HLA interactions modulate genetic risk for multiple sclerosis

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H;

    2015-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17......,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles...... (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA...

  3. Clinical implication of HLA class I expression in breast cancer

    International Nuclear Information System (INIS)

    Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified. A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed. The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval. The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system

  4. HLA-E: Presentation of a Broader Peptide Repertoire Impacts the Cellular Immune Response—Implications on HSCT Outcome

    Directory of Open Access Journals (Sweden)

    Thomas Kraemer

    2015-01-01

    Full Text Available The HLA-E locus encodes a nonclassical class Ib molecule that serves many immune functions from inhibiting NK cells to activating CTLs. Structural analysis of HLA-E/NKG2A complexes visualized fine-tuning of protective immune responses through AA interactions between HLA-E, the bound peptide, and NKG2A/CD94. A loss of cellular protection through abrogation of the HLA-E/NKG2A engagement is dependent on the HLA-E bound peptide. The role of HLA-E in posttransplant outcomes is not well understood but might be attributed to its peptide repertoire. To investigate the self-peptide repertoire of HLA-E∗01:01 in the absence of protective HLA class I signal peptides, we utilized soluble HLA technology in class I negative LCL cells in order to characterize HLA-E∗01:01-bound ligands by mass-spectrometry. To understand the immunological impact of these analyzed ligands on NK cell reactivity, we performed cellular assays. Synthesized peptides were loaded onto recombinant T2 cells expressing HLA-E∗01:01 molecules and applied in cytotoxicity assays using the leukemia derived NK cell line (NKL as effector. HLA-E in complex with the self-peptides demonstrated a shift towards cytotoxicity and a loss of cell protection. Our data highlights the fact that the HLA-E-peptidome is not as restricted as previously thought and support the suggestion of a posttransplant role for HLA-E.

  5. A common minimal motif for the ligands of HLA-B*27 class I molecules.

    Directory of Open Access Journals (Sweden)

    Alejandro Barriga

    Full Text Available CD8(+ T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

  6. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy

    DEFF Research Database (Denmark)

    Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang;

    2015-01-01

    Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza...... H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA...... loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and...

  7. Class II HLA antigens in multiple sclerosis.

    Science.gov (United States)

    Miller, D H; Hornabrook, R W; Dagger, J; Fong, R

    1989-01-01

    HLA typing in Wellington revealed a stronger association of multiple sclerosis with DR2 than with DQw1. The association with DQw1 appeared to be due to linkage disequilibrium of this antigen with DR2. These results, when considered in conjunction with other studies, are most easily explained by the hypothesis that susceptibility to multiple sclerosis is influenced by multiple risk factors, with DR2 being an important risk factor in Caucasoid populations. PMID:2732726

  8. Oligoclonal band phenotypes in MS differ in their HLA class II association, while specific KIR ligands at HLA class I show association to MS in general

    DEFF Research Database (Denmark)

    Gustavsen, Marte W; Viken, Marte K; Celius, Elisabeth G;

    2014-01-01

    Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated the...... association of HLA alleles and KIR ligands according to OCB status in MS patients (n=3876). Specific KIR ligands were associated with patients when compared to controls (n=3148), supporting a role for NK cells in MS pathogenesis. HLA class I alleles and KIR ligands did not differ between OCB phenotypes, but...... HLA class II associations were convincingly replicated....

  9. 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*02:0...... both HLA class I and class I restricted responses, a quality which might be of potential interest for peptide-based vaccine development....

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    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...... 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...

  11. HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

    OpenAIRE

    M A Brown; Pile, K D; Kennedy, L G; Calin, A.; Darke, C; Bell, J.; Wordsworth, B P; Cornélis, F

    1996-01-01

    OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically mat...

  12. Mutations in the HLA class II genes leading to loss of expression of HLA-DR and HLA-DQ in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Jordanova, ES; Philippo, K; Giphart, MJ; Schuuring, E; Kluin, PM

    2003-01-01

    Loss of expression of human leukocyte antigen (HLA) class II molecules on tumor cells affects the onset and modulation of the immune response through lack of activation of CD4(+) T lymphocytes. Previously, we showed that the frequent loss of expression of HLA class II in diffuse large B-cell lymphom

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

    OpenAIRE

    Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren; Rasmussen, Michael; Korsholm, Karen Smith; Nielsen, Morten; Claesson, Mogens Helweg

    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 ...

  14. Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

    DEFF Research Database (Denmark)

    Lund, Ole; Nascimento, Eduardo J. M.; Maciel, Milton, Jr;

    2011-01-01

    Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV...... epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 500 nM. The immunogenicity of 25 HLA......-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non-immunogenic peptides...

  15. The Association of HLA-Class I and Class II with Hodgkin’s Lymphoma in Iranian Patients

    OpenAIRE

    Arezou Sayad; Mohammad Taghi Akbari; Mahshid Mehdizadeh; Abolfazl Movafagh; Abbas Hajifathali

    2014-01-01

    The Hodgkin's lymphoma disease (HD) is a common malignant neoplasm with germinal centre B-cell origin. It has been suggested that the HLA class I and class II regions have susceptibility effects on HD. In different ethnic groups, different HLA class I and class II alleles affect HD. As a result, there is no consensus which of the different HLA alleles confers susceptibility to HD. In this study, we aimed to ascertain the role of HLA class I and class II alleles in association with Hodgkin's l...

  16. Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

    DEFF Research Database (Denmark)

    Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper;

    2009-01-01

    The Human MHC Project aims at large-scale description of peptide-HLA binding to a wide range of HLA molecules covering all populations of the world and the accompanying generation of bioinformatics tools capable of predicting binding of any given peptide to any given HLA molecule. Here, the authors...... present a homogenous, proximity-based assay for detection of peptide binding to HLA class I molecules. It uses a conformation-dependent anti-HLA class I antibody, W6/32, as one tag and a biotinylated recombinant HLA class I molecule as the other tag, and a proximity-based signal is generated through the...... luminescent oxygen channeling immunoassay technology (abbreviated LOCI and commercialized as AlphaScreen (TM)). Compared with an enzyme-linked immunosorbent assay-based peptide-HLA class I binding assay, the LOCI assay yields virtually identical affinity measurements, although having a broader dynamic range...

  17. Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

    OpenAIRE

    Mehta, Akash M.; Jordanova, Ekaterina S.; Kenter, Gemma G; Ferrone, Soldano; Fleuren, Gert- Jan

    2007-01-01

    HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin,...

  18. Vaccination and Infection as Causative Factors in Japanese Patients With Rasmussen Syndrome: Molecular Mimicry and HLA Class I

    Directory of Open Access Journals (Sweden)

    Yukitoshi Takahashi

    2006-01-01

    Full Text Available Rasmussen syndrome is an intractable epilepsy with a putative causal relation with cellular and humoral autoimmunity. Almost half of the patients have some preceding causative factors, with infections found in 38.2%, vaccinations in 5.9% and head trauma in 8.9% of Japanese patients. In a patient with seizure onset after influenza A infections, cross-reaction of the patient's lymphocytes with GluRε2 and influenza vaccine components was demonstrated by lymphocyte stimulation test. Database analyses revealed that influenza A virus hemagglutinin and GluRε2 molecules contain peptides with the patient's HLA class I binding motif (HLA ࢤ A*0201. The relative risks of HLA class I genotypes for Rasmussen syndrome are 6.1 (A*2402, 6.4 (A*0201, 6.3 (A*2601 and 11.4 (B*4601. The relative risks of HLA class I-A and B haplotypes are infinity (A*2601+B*5401, 21.1 (A*2402+B*1501, 13.3 (A*2402+B*4801 and 5.1 (A*2402+B*5201. Some alleles and haplotypes of HLA class I may be the risk factors in Japanese patients. Cross-reactivity of cytotoxic T lymphocytes may contribute to the processes leading from infection to the involvement of CNS.

  19. EXPRESSION OF HLA-CLASS Ⅱ GENESOF IDDM PATIENTS ON THE SURFACE OF THE LTK- CELLS

    Institute of Scientific and Technical Information of China (English)

    王姮; 孙琦

    1994-01-01

    To investigate the function of HLA-class Ⅱ genes in the autoimmune response of insulin dependent diabetes mellitus(DDM),the HLA-class Ⅱ gene of IDDM patients was introd uced into Ltk-cells with pSV2-neo plas-mid,using the calcium phosphate precipitation technique.We obtained a stable cell line expressing the HLA-class Ⅱ gene from lymphocytes of IDDM patients.Expression was identified by direct ox erythocyte-CrCl3-HLA DR monoclonal antibody rosetting.

  20. HLA Class II Haplotypic Association and DQCAR Microsatellite Polymorphisms in Croatian Patients with Psoriasis

    OpenAIRE

    Grubić, Z.; Žunec, R.; Kaštelan, M.; Čečuk-Jeličić, E.; Gruber, F; Kaštelan, A.

    2002-01-01

    The purpose of the present study was to investigate polymorphism of HLA class II haplotypic associations (HLA-DRB1, -DQA1, -DQB1) and DQCAR alleles in 78 Croatian patients with psoriasis. Patients were divided into two groups according to a family history of disease and age of onset: type I (positive family history and early onset) and type II (negative family history and late onset). The difference in frequency of HLA class II haplotypic associations between type I patients an...

  1. Impact of HLA class I restricted T cells on HIV-1 disease progression

    NARCIS (Netherlands)

    Schellens, I.M.M.

    2009-01-01

    This thesis focuses on the impact of HLA class I restricted T cells on HIV-1 disease progression. It is generally accepted that cytotoxic T lymphocytes (CTL) play an important role in controlling HIV replication. In line with this, it has been well established that HLA class I alleles influence the

  2. Human HLA class I- and HLA class II-restricted cloned cytotoxic T lymphocytes identify a cluster of epitopes on the measles virus fusion protein.

    Science.gov (United States)

    van Binnendijk, R S; Versteeg-van Oosten, J P; Poelen, M C; Brugghe, H F; Hoogerhout, P; Osterhaus, A D; Uytdehaag, F G

    1993-01-01

    The transmembrane fusion (F) glycoprotein of measles virus is an important target antigen of human HLA class I- and class II-restricted cytotoxic T lymphocytes (CTL). Genetically engineered F proteins and nested sets of synthetic peptides spanning the F protein were used to determine sequences of F recognized by a number of F-specific CTL clones. Combined N- and C-terminal deletions of the respective peptides revealed that human HLA class I and HLA class II-restricted CTL efficiently recognize nonapeptides or decapeptides representing epitopes of F. Three distinct sequences recognized by three different HLA class II (DQw1, DR2, and DR4/w53)-restricted CTL clones appear to cluster between amino acids 379 and 466 of F, thus defining an important T-cell epitope area of F. Within this same region, a nonamer peptide of F was found to be recognized by an HLA-B27-restricted CTL clone, as expected on the basis of the structural homology between this peptide and other known HLA-B27 binding peptides. PMID:7680390

  3. HLA class I and class II haplotypes in admixed families from several regions of Mexico.

    Science.gov (United States)

    Barquera, Rodrigo; Zúñiga, Joaquín; Hernández-Díaz, Raquel; Acuña-Alonzo, Victor; Montoya-Gama, Karla; Moscoso, Juan; Torres-García, Diana; García-Salas, Claudia; Silva, Beatriz; Cruz-Robles, David; Arnaiz-Villena, Antonio; Vargas-Alarcón, Gilberto; Granados, Julio

    2008-02-01

    We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA-A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies. PMID:17904223

  4. Relationship between the downregulation of HLA class I antigen and clinicopathological significance in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yu-Qing Shen; Jian-Qiong Zhang; Feng-Qing Miao; Jian-Min Zhang; Qin Jiang; Hao Chen; Xiang-Nian Shan; Wei Xie

    2005-01-01

    AIM: To discuss the expression of human leukocyte antigen (HLA) class I antigens in gastric cancer and correlate these with pathologic type and TNM stage.METHODS: The expression of HLA class I antigen was detected by immunohistochemistry in 185 specimens of gastric cancer, 20 gastric cancer specimens with lymphatic metastasis and 22 controls of normal gastric mucosa using four monoclonal antibodies.RESULTS: The expression of HLA class I antigen (B/C locus) was significantly downregulated in gastric cancer and in lymphatic metastasis than that in normal gastricmucosa (x2 = 7.712, P<0.05). The expression of other HLA class I antigens was also downregulated, but the change was slight. There was no relationship betweenthe downregulation of HLA class I antigen and that ofβ2m and LMP2. The expression of HLA class I (B/C locus) was statistically correlated with pathologic stage in gastric adenocarcinoma (x2= 4.164, P<0.05).CONCLUSION: The expression of HLA class I antigen (B/Clocus) was obviously downregulated in gastric cancer andin lymphatic metastasis. This abnormal expression wouldprovide the tumor cells with a way to avoid immunologicalrecognition.

  5. NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ

    DEFF Research Database (Denmark)

    Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas;

    2013-01-01

    become particularly attractive as first-line methods in epitope discovery. However, only a few so-called pan-specific prediction methods capable of predicting binding to any MHC molecule with known protein sequence are currently available, and all of them are limited to HLA-DR. Here, we present the first...... pan-specific method capable of predicting peptide binding to any HLA class II molecule with a defined protein sequence. The method employs a strategy common for HLA-DR, HLA-DP and HLA-DQ molecules to define the peptide-binding MHC environment in terms of a pseudo sequence. This strategy allows the......MHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0....

  6. Machine learning competition in immunology – Prediction of HLA class I binding peptides

    DEFF Research Database (Denmark)

    Zhang, Guang Lan; Ansari, Hifzur Rahman; Bradley, Phil;

    2011-01-01

    ., 2008] and [Larsen et al., 2010]). HTMS involves HLA typing, immunoaffinity chromatography of HLA molecules, HLA extraction, and chromatography combined with tandem mass spectrometry, followed by the application of computational algorithms for peptide characterization (Bassani-Sternberg et al., 2010......). Hundreds of naturally processed HLA class I associated peptides have been identified in individual studies using HTMS in normal (Escobar et al., 2008), cancer ( [Antwi et al., 2009] and [Bassani-Sternberg et al., 2010]), autoimmunity-related (Ben Dror et al., 2010), and infected samples (Wahl et al, 2010...... of peptide binding, therefore, determines the accuracy of the overall method. Computational predictions of peptide binding to HLA, both class I and class II, use a variety of algorithms ranging from binding motifs to advanced machine learning techniques ( [Brusic et al., 2004] and [Lafuente and Reche...

  7. Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles

    OpenAIRE

    De la Hera, Belén; Urcelay, Elena; Brassat, David; Chan, Andrew; Vidal-Jordana, Angela; Salmen, Anke; Villar, Luisa Maria; Álvarez-Cermeño, José Carlos; Izquierdo, Guillermo; Fernández, Oscar; Oliver, Begoña; Saiz, Albert; Ara, Jose Ramón; Vigo, Ana G.; Arroyo, Rafael

    2014-01-01

    Objectives: We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. Methods: HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. Results:...

  8. A detailed comparison of peptides presented by different HLA class I loci: an in silico approach

    NARCIS (Netherlands)

    Rao, X.

    2012-01-01

    Human Leukocyte Antigen (HLA) class I is a group of genes located on human chromosome 6 which play a crucial role in initiating potentially protective immune responses, by presenting pathogen-derived peptides to CD8+ T cells and thus targeting infected cells for elimination. Compare to other HLA cla

  9. HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1

    OpenAIRE

    de la Salle, Henri; Zimmer, Jacques; Fricker, Dominique; Angenieux, Catherine; Cazenave, Jean-Pierre; Okubo, Mitsuo; Maeda, Hiroo; Plebani, Alessandro; Tongio, Marie-Marthe; Dormoy, Anne; Hanau, Daniel

    1999-01-01

    The transporter associated with antigen processing (TAP), which is composed of two subunits (TAP1 and TAP2) that have different biochemical and functional properties, plays a key role in peptide loading and the cell surface expression of HLA class I molecules. Three cases of HLA class I deficiency have previously been shown to result from the absence of a functional TAP2 subunit. In the present study, we analyzed two cases displaying not only the typical lung syndrome of HLA class I deficienc...

  10. Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells

    DEFF Research Database (Denmark)

    Ternette, Nicola; Yang, Hongbing; Partridge, Thomas;

    2016-01-01

    Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding...... time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4+ T cells and the C8166 human T-cell line. Importantly, one-third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I...

  11. Data on HLA class I/II profile in Brazilian pemphigus patients.

    Science.gov (United States)

    Franco Brochado, Maria José; Nascimento, Daniela Francisca; Saloum Deghaide, Neifi Hassan; Donadi, Eduardo Antonio; Roselino, Ana Maria

    2016-09-01

    Pemphigus are blistering autoimmune diseases related with genetic and environmental factors. Here we describe HLA genotyping in pemphigus patients. First, we review the HLA class I/II data on pemphigus reported in Brazilian samples and then present the HLA class I (-A, -B, -C) and class II (-DRB1, -DQA1, -DQB1) alleles related to susceptibility/resistance to pemphigus by comparing 86 patients with pemphigus foliaceus, 83 patients with pemphigus vulgaris, and 1592 controls from the northeastern region of the state of São Paulo, Southeastern Brazil. The data presented here are related to the manuscript "Differential HLA class I and class II associations in Pemphigus Foliaceus and Pemphigus Vulgaris patients from a prevalent Southeastern Brazilian region" Brochado et al. (2016) [1]. PMID:27331116

  12. LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Arman A Bashirova

    2014-03-01

    Full Text Available Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1 by changing interactions of human leukocyte antigen (HLA class I molecules with leukocyte immunoglobulin-like receptors (LILR, a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs. We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126 to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2. Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11-10(-9 and African (p = 10(-5-10(-3 descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.

  13. Protective and Susceptible HLA Class I Genes in Patients with End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    2008-01-01

    Full Text Available The role of the HLA system in the pathophysiology of primary renal disease is intriguing, but not completely resolved. According to the results of studies links between HLA haplotype and renal failure has been reported. This study was conducted to determine protective and susceptible role of HLA class I genes in end stage renal disease patients. Subjects of this study were 77 individuals from Azerbaijan republic referred to Iran Red Crescent Society clinic in Baku of which were assigned into 2 group, case and control, based on renal disease. Case group were 26 patients with end stage renal disease candidate for renal transplant and controls were 51 healthy subjects. Typing of HLA class I was performed by serologic method. There was no significant difference in age and sex between control and patient groups. The most frequent detected HLA antigens were A2 (41.6%, A3(28.6%, A24(26% from A loci and B35 (46.8%, B51 (29.9%, B18 (13% from B loci. Significant association was found between susceptibility to ESRD and HLA-A33, A11, B49 (p<0.05. The findings support the idea that polymorphism of HLA class I may influence the susceptibility to ESRD. We suggested HLA antigen distribution will identify the high-risk patients who are candidates for transplantation.

  14. Cytomegalovirus Infection in Ireland: Seroprevalence, HLA Class I Alleles, and Implications.

    Science.gov (United States)

    Hassan, Jaythoon; O'Neill, Derek; Honari, Bahman; De Gascun, Cillian; Connell, Jeff; Keogan, Mary; Hickey, David

    2016-02-01

    Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss.We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type.The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22-48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31.2%, and 30.8%, respectively. The presence of the most common inherited haplotype in the Irish population, HLA-A1, B8 was significantly associated with CMV seronegativity (OR = 1.278, P HLA-A1 in the Irish population may, in part, have a role in the reduced susceptibility to CMV infection. PMID:26871815

  15. Diversity of natural self-derived ligands presented by different HLA class I molecules in transporter antigen processing-deficient cells.

    Directory of Open Access Journals (Sweden)

    Elena Lorente

    Full Text Available The transporter associated with antigen processing (TAP translocates the cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen where they complex with nascent human leukocyte antigen (HLA class I molecules. Non-functional TAP complexes and viral or tumoral blocking of these transporters leads to reduced HLA class I surface expression and a drastic change in the available peptide repertoire. Using mass spectrometry to analyze complex human leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP-deficient cells, we identified 334 TAP-independent ligands naturally presented by four different HLA-A, -B, and -C class I molecules with very different TAP dependency from the same cell line. The repertoire of TAP-independent peptides examined favored increased peptide lengths and a lack of strict binding motifs for all four HLA class I molecules studied. The TAP-independent peptidome arose from 182 parental proteins, the majority of which yielded one HLA ligand. In contrast, TAP-independent antigen processing of very few cellular proteins generated multiple HLA ligands. Comparison between TAP-independent peptidome and proteome of several subcellular locations suggests that the secretory vesicle-like organelles could be a relevant source of parental proteins for TAP-independent HLA ligands. Finally, a predominant endoproteolytic peptidase specificity for Arg/Lys or Leu/Phe residues in the P(1 position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways.

  16. The HLA Class II Associations with Rheumatic Heart Disease in South Indian Patients: A Preliminary Study

    OpenAIRE

    Bajoria, Divya; Menon, Thangam

    2013-01-01

    Introduction: Rheumatic heart disease (RHD) occurs in 30-45% of the patients with rheumatic fever (RF) and it leads to chronic valvular lesions. The human leukocyte antigen (HLA) might confer a susceptibility to RHD. The aim of the present study was to determine the prevalent HLA class II DR/DQ allelic types which were associated with rheumatic heart disease (RHD) in a small group of south Indian patients and to compare them with those in the control subjects.

  17. The human amnion is a site of MHC class lb expression: Evidence for the expression of HLA-E and HLA-G

    Energy Technology Data Exchange (ETDEWEB)

    Houlihan, J.M.; Harper, H.M.; Jenkinson, H.J. [Univ. of Bristol (United Kingdom)] [and others

    1995-06-01

    The expression of HLA class I Ag by term human amnion epithelial cells was investigated. In immunostaining and FACS analysis, mAb to monomorphic class I Ag reacted extensively with amnion cells, whereas polymorphic mAb reactivity was more limited and variable. Further studies were conducted on amnion cell preparations containing negligible contaminants. Northern analysis with use of locus-specific probes demonstrated that amnion expresses two class lb genes, HLA-E and HLA-G. Radio-immunoprecipitation with use of monomorphic mAb identified two fully glycosylated cell surface class I H chains of 44 and 41 kDa; polymorphic mAbs failed to immunoprecipitate the 41-kDa product, although 44-kDa products, typical of class la Ag, were identified in some preparations. Class I H chains were isolated from amnion by affinity chromatography. Microsequencing revealed that the first nine residues of the N-terminus of the 41-kDa product aligned perfectly only with HLA-E. Overall, amnion at term appears to express class lb Ag with limited class la Ag. HLA-G is therefore expressed in two extrafetal epithelia: amnion and trophoblast. Identification of the class lb protein HLA-E-E in amnion epithelium may have implications for preterm labor that can be associated with infection of the placental membranes. 44 refs., 5 figs., 2 tabs.

  18. HLA Class II Allele and Haplotype Frequencies in Iranian Patients with Leukemia

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    Farideh Khosravi

    2007-09-01

    Full Text Available Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML" and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033. Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%. According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls .In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.

  19. Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation.

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    Eva Zilian

    Full Text Available Antibody-mediated rejection (AMR is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA class I (HLA I antibodies (Abs play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs. The antioxidant enzyme heme oxygenase (HO-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

  20. Extensive HLA class Ⅱ studies in Chinese narcoleptic patients.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: Narcolepsy is a debilitating, lifelong sleep disorder. Its familial occurrence suggests that genetic factors may be of importance in the etiology. Narcolepsy is a very rare disease among Chinese, thus it was of interest to study the association of narcolepsy with the HLA system in Chinese narcoleptic patients.

  1. Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction.

    Science.gov (United States)

    Hirabayashi, Koichi; Kurata, Takashi; Horiuchi, Kazuki; Saito, Shoji; Shigemura, Tomonari; Tanaka, Miyuki; Yanagisawa, Ryu; Matsuda, Kazuyuki; Sakashita, Kazuo; Koike, Kenichi; Nakazawa, Yozo

    2016-04-01

    Mechanisms of relapse of acute lymphoblastic leukemia (ALL) after human leukocyte antigen (HLA) class II mismatched hematopoietic stem cell transplantation (HSCT) remain unclear. We report two children with relapsed ALL after HSCT from related donors with HLA-DRB1 and -DQB1 mismatches in the graft versus host direction. One lost HLA-DRB1, DQB1, and DPB1 alleles, and the other lost one HLA haplotype of the leukemic blasts at relapse. HLA class II loss may be a triggering event for ALL relapse after partially HLA-mismatched-related HSCT. In addition, HLA typing of relapsed leukemic blasts could be vital in the selection of retransplant donors. PMID:26544669

  2. Frequency of class I anti-HLA alloantibodies in patients infected by HIV-1

    Directory of Open Access Journals (Sweden)

    Elza Regina Manzolli Leite

    2010-02-01

    Full Text Available The aim of this study was to evaluate the presence of class I anti-HLA alloantibodies in patients infected by HIV-1 and relate it with the different clinical courses of the disease. Blood samples were collected in EDTA tubes from 145 individuals. HIV-1 infection was confirmed by ELISA test. The presence of class I anti-HLA alloantibodies and HLA allele's were determined. Clinical evolution was set as fast (3 years. Class I anti-HLA alloantibodies presence was lower in healthy individuals than in those infected by HIV-1 (4.2% against 32.4%. However, an equal distribution of these alloantibodies was found among the individuals infected, independent on the clinical evolution. Thus, class I anti-HLA alloantibodies was not a determinant factor for patient worsening.O objetivo deste estudo foi avaliar a presença de aloanticorpos anti-HLA classe I em pacientes infectados pelo HIV-1 e relacioná-la aos diferentes cursos clínicos da doença. Amostras de sangue de 145 indivíduos HIV positivo foram coletadas em tubos com EDTA. A infecção pelo HIV-1 foi confirmada por teste ELISA e a presença de aloanticorpos anti-HLA classe I determinada em seguida. A evolução clínica foi definida como rápida (3 anos. A presença de aloanticorpos anti-HLA classe I foi menor em indivíduos saudáveis em relação aos infectados pelo HIV-1 (4,2% contra 32,4%. Porém, a distribuição destes aloanticorpos entre os indivíduos infectados foi igual, independente da evolução clínica. Deste modo, a presença de aloanticorpos anti-HLA classe I não é um fator determinante na piora clínica do paciente.

  3. Role of HLA class I antigens in the development of psoriatic arthritis and its clinical presentation

    Directory of Open Access Journals (Sweden)

    Irina Aleksandrovna Troshkina

    2012-01-01

    Full Text Available Objective: to investigate the association of HLA Class I antigens with the predisposition to psoriatic arthritis (PsA and the severity and types of articular syndrome in PsA. Subjects and methods. The investigation enrolled 99 patients (56 females and 43 males aged 43.5+13 years with PA with a median duration of 2 (range 0.8-10 years. An oligoarthritic type was observed in 28 patients, polyarthritic, distal, and spondyloarthritic types were present in 28, 39, and 10 patients, respectively. Two patient groups were formed according to the age at onset of psoriasis: 1 71 patients aged less than 40 years and 2 23 patients aged over 40 years. Results. As compared with the control group, the patients with PsA were found to have a higher frequency of HLA-B13 (odds ratio [OR] 2.72; p < 0.004, HLA-В16 (OR 3.95; p < 0.0001, and HLA-B27 (OR 3.2; p < 0.003. There was an association of the types of joint injury with HLA antigens: the distal type with HLA-B13 (OR 3.38; p < 0.02 and HLA-В16 (OR 3.95; p < 0.01, the polyarthritic type with HLA-В16 (OR 5.90; p < 0.0001 and HLA-B27 (OR 3.26; p < 0.01, and the spondyloarthritic type with HLA-B27 (OR 6.32; p < 0.001. The young onset of psoriasis was associated with HLA-B13 (OR 3.29; p < 0.001. The detection rate of the B38 antigen (the subtype of HLA-B16 was higher in all X-ray stages of PsA and was 16.4% in Stages I-IIA, 25% in Stage IIB, and 40.9% in Stages III-IV versus 8.7% in the control group, the magnitude of the association being increased with the higher degree of joint destruction. Conclusion. The detailed analysis of the investigation revealed that HLA system antigens were differently involved in the development of PsA and clinical types of articular syndrome.

  4. Functional role of HLA class I cell-surface molecules in human T-lymphocyte activation and proliferation.

    OpenAIRE

    Taylor, D S; Nowell, P C; Kornbluth, J

    1986-01-01

    This investigation addressed the role of major histocompatibility complex-encoded class I molecules in the activation and proliferation of human lymphocytes. We studied the effect of antibodies specific for HLA-A and HLA-B locus gene products on mitogen-stimulated peripheral blood mononuclear cell (PBMC) subpopulations. Three individually derived, well-characterized anti-HLA class I monoclonal antibodies were demonstrated to inhibit the proliferation of human PBMC stimulated by either OKT3 or...

  5. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However, the...... barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce this...... complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  6. HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma

    NARCIS (Netherlands)

    Diepstra, Arjan; van Imhoff, Gustaaf W.; Karim-Kos, Henrike E.; van den Berg, Anke; te Meerman, Gerard J.; Niens, Marijke; Nolte, Ilja M.; Bastiaannet, Esther; Schaapveld, Michael; Vellenga, Edo; Poppema, Sibrand

    2007-01-01

    Purpose The neoplastic Hodgkin Reed-Sternberg ( HRS) cells in classical Hodgkin's lymphoma ( cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown. Patients and Methods Immunohistochemistry results for HLA class II were evaluated in 292 p

  7. HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice

    DEFF Research Database (Denmark)

    Boucherma, Rachid; Kridane-Miledi, Hédia; Bouziat, Romain;

    2013-01-01

    We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas...... surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed...... a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either...

  8. Typing of HLA class II and class I antigens using PHA-activated, IL-2-propagated T lymphocytes.

    Science.gov (United States)

    Leshem, B; Cohen, I; Sherman, L; Brautbar, C; Kedar, E

    1988-06-28

    We describe here a simple procedure, by which HLA class II antigens can be accurately and reliably identified in those patients where there is minimal or absent expression of HLA-DR,DQw antigens on B cells, or when the total number of leukocytes recovered from the patients do not permit reliable typing. Ficoll-Hypaque-separated peripheral blood mononuclear leukocytes, fresh or cryopreserved, were activated by PHA and then propagated in IL-2-containing medium until enough cells for typing were obtained (usually 7-14 days). At this stage, the cultured cells were shown to be primarily T cells (greater than 90% CD3+). Since the activated T cells propagate in the presence of IL-2, even a small number (10(4] of fresh or cryopreserved patients' cells suffice for this protocol. To date we have been able to successfully HLA-DR,DQw type 34/34 bone marrow transplantation candidates and 12/12 long-term dialysis patients, who were untypable using fresh cells. HLA-DR,DQw antigens on activated T cells from normal individuals were identical to those found on their uncultured B cells. In addition, class I antigens that were undetectable on the uncultured cells of one patient could be identified on activated T cells. The HLA antigens identified on the patients' activated T cells were confirmed by phenotypic analysis of cells from family members. PMID:3260612

  9. The Cancer Exome Generated by Alternative mRNA Splicing Dilutes Predicted HLA Class I Epitope Density

    DEFF Research Database (Denmark)

    Stranzl, Thomas; Larsen, Mette Voldby; Lund, Ole;

    2012-01-01

    is frequently observed in various types of cancer. Down-regulation of genes related to HLA class I antigen processing has been observed in several cancer types, leading to fewer HLA class I antigens on the cell surface. Here, we use a peptidome wide analysis of predicted alternative splice forms, based...... on a publicly available database, to show that peptides over-represented in cancer splice variants comprise significantly fewer predicted HLA class I epitopes compared to peptides from normal transcripts. Peptides over-represented in cancer transcripts are in the case of the three most common HLA class I......Several studies have shown that cancers actively regulate alternative splicing. Altered splicing mechanisms in cancer lead to cancer-specific transcripts different from the pool of transcripts occurring only in healthy tissue. At the same time, altered presentation of HLA class I epitopes...

  10. High resolution human leukocyte antigen (HLA class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    Directory of Open Access Journals (Sweden)

    Barquera Rodrigo

    2009-02-01

    Full Text Available Abstract Background The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA alleles play an important role in immunity (cellular immunity and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. Methods We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. Results HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031. HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670. DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001. Conclusion Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the

  11. High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    International Nuclear Information System (INIS)

    The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA

  12. Association between HLA class Ⅱ gene and susceptibility or resistance to chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ye-Gui Jiang; Yu-Ming Wang; Tong-Hua Liu; Jun Liu

    2003-01-01

    AIM: To investigate the association between the polymorphism of HLA-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B.METHODS: HLA-DRB1, -DQA1 and -DQB1 alleles in 54patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique.RESULTS: The allele frequency of HLA-DRB1*0301 in the chronic hepatitis B group was markedly higher than that in the normal control group (17.31% VS 5.67%), there was a significant correlation between them (χ2= 12.3068,Pc=0.0074, RR=4.15). The allele frequency of HLADQA1*0501 in the chronic hepatitis B group was significantly higher than that in the normal control group (25.96% VS 13.68%), there was a significant correlation between them (χ2=9.2002, PC=0.0157, RR=2.87). The allele frequency of HLA-DQB1*0301 in the chronic hepatitis B group was notably higher than that in the normal control group (35.58%vs 18.87%), there was a significant correlation between them (χ2=15.5938, PC=0.0075, RR=4.07). The allele frequency of HLA-DRB1*1101/1104 in the chronic hepatitis B group was obviously lower than that in the normal control group (0.96% VS 13.33%), there was a significant correlation between them (χ2=11.9206, PC=0.0145, RR=18.55). The allele frequency of HLA-DQA1*0301 in the chronic hepatitis B group was remarkably lower than that in the normal control group (14.42% VS30%), there was a significant correlation between them (χ2=8.7396, Pc=0.0167, RR=0.35).CONCLUSION: HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0301 are closely related with susceptibility to chronic hepatitis B, and HLA-DRB1*1101/1104 and HLADQA1*0301 are closely related with resistance to chronic hepatitis B. These findings suggest that host HLA class Ⅱ gene is an important factor determining the outcome of HBV infection.

  13. PML nuclear bodies and SATB1 are associated with HLA class I expression in EBV+ Hodgkin lymphoma.

    Directory of Open Access Journals (Sweden)

    Yuxuan Liu

    Full Text Available Tumor cells of classical Hodgkin lymphoma (cHL are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML and special AT-rich region binding protein 1 (SATB1 are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV- cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV- cases (p<0.0001. We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV- cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV- cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01. The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05. Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL.

  14. Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Rana J EI Wafai

    2011-01-01

    Full Text Available Type-1 diabetes mellitus (T1DM is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting β-cells of the pancreas. HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1], especially DR and DQ, show strong association with T1DM. In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12 on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes. The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP technique and to investigate the asso-ciation of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis in Lebanese T1DM patients. The study was conduc-ted on 39 Lebanese T1DM patients. Results of HLA typing showed an increased frequency of the HLA-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 alleles, sugges-ting risk association and thus can be considered as susceptibility alleles. On the other hand, strong protection against the disease was conferred by the HLA-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 alleles. RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population. Analysis of the two polymorphisms showed no detectable association between the two genes. However, a significant negative association of the G allele with the DQB1FNx010201 allele was ob-served. This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.

  15. Human papillomavirus type 16 (HPV-16 E5 protein and HLA class I

    Directory of Open Access Journals (Sweden)

    MR Haghshenas

    2005-10-01

    Full Text Available Human papillomavirus type 16 E5 protein (HPV16 E5 is expressed early in papillomavirus infection in the deep layers of the infected epithelium, and is localised primarily in the cell Golgi apparatus (GA and endoplasmic reticulum (ER. We have shown that E5 prevents transport of the major histocompatibility class I (MHC I to the cell surface and retains the complex in the GA. Here we show that these effects are due, at least in part, to the interaction between E5 and many types of MHC I heavy chain (Hc. In addition, we have further investigated the domain necessary to down-regulate surface MHC I and to interact with Hc, by using deletion mutants of E5, including either helical domain 1, 2 or 3. We show that the down-regulation of surface MHC I (HLA I in humans, and interaction with Hc are mediated by the first helical domain of E5. Although E5 down-regulates classical HLA selectively as it does not down-regulate non-classical HLA (ref. 4, the interaction with the Hc of classical HLA I is not specific for a particular type of HLA I, suggesting that E5 can interfere with antigen presentation by most, if not all, of classical HLA I types. The down-regulation of HLA I can potentially have serious consequences for the host immune response to viral infection, as the ability of infected cells to present antigenic peptides to effector T cells would be compromised.

  16. Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their correlation with HLA matches and acute cellular rejection

    Directory of Open Access Journals (Sweden)

    Ana Carolina Guardia

    2014-04-01

    Full Text Available Herpesvirus reactivation is common after liver transplantation. OBJECTIVE: Analyze the presence of cytomegalovirus (HCMV and human herpesvirus-6 (HHV-6 DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA-A, B and DR, as well as correlations with acute cellular rejection. METHODS: Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied. RESULTS: Seven (11.8% biopsies were positive for HCMV DNA and 29 (49% were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09, 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ 2=4.51, which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08. CONCLUSION: HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.

  17. HNPCC versus sporadic microsatellite-unstable colon cancers follow different routes toward loss of HLA class I expression

    International Nuclear Information System (INIS)

    Abnormalities in Human Leukocyte Antigen (HLA) class I expression are common in colorectal cancer. Since HLA expression is required to activate tumor antigen-specific cytotoxic T-lymphocytes (CTL), HLA class I abnormalities represent a mechanism by which tumors circumvent immune surveillance. Tumors with high microsatellite instability (MSI-H) are believed to face strong selective pressure to evade CTL activity since they produce large amounts of immunogenic peptides. Previous studies identified the prevalence of HLA class I alterations in MSI-H tumors. However, those reports did not compare the frequency of alterations between hereditary and sporadic MSI-H tumors neither the mechanisms that led to HLA class I alterations in each subgroup. To characterize the HLA class I expression among sporadic MSI-H and microsatellite-stable (MSS) tumors, and HNPCC tumors we compared immunohistochemically the expression of HLA class I, β2-microglobulin (β2m), and Antigen Processing Machinery (APM) components in 81 right-sided sporadic and 75 HNPCC tumors. Moreover, we investigated the genetic basis for these changes. HLA class I loss was seen more frequently in MSI-H tumors than in MSS tumors (p < 0.0001). Distinct mechanisms were responsible for HLA class I loss in HNPCC and sporadic MSI-H tumors. Loss of HLA class I expression was associated with β2m loss in HNPCC tumors, but was correlated with APM component defects in sporadic MSI-H tumors (p < 0.0001). In about half of the cases, loss of expression of HLA class I was concordant with the detection of one or more mutations in the β2m and APM components genes. HLA class I aberrations are found at varying frequencies in different colorectal tumor types and are caused by distinct genetic mechanisms. Chiefly, sporadic and hereditary MSI-H tumors follow different routes toward HLA class I loss of expression supporting the idea that these tumors follow different evolutionary pathways in tumorigenesis. The resulting variation in

  18. The Leukocyte Immunoglobulin-Like Receptor Family Member LILRB5 Binds to HLA-Class I Heavy Chains.

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    Zhiyong Zhang

    Full Text Available The leukocyte immunoglobulin-like receptor (LILR family includes inhibitory and stimulatory members which bind to classical and non-classical HLA-class I. The ligands for many LILR including LILRB5 have not yet been identified.We generated C-terminal eGFP and N-terminal FLAG-tagged fusion constructs for monitoring LILR expression. We screened for LILR binding to HLA-class I by tetramer staining of 293T cells transfected with LILRA1, A4, A5 A6 and LILRB2 and LILRB5. We also studied HLA class I tetramer binding to LILRB5 on peripheral monocyte cells. LILRB5 binding to HLA-class I heavy chains was confirmed by co-immunoprecipitation.HLA-B27 (B27 free heavy chain (FHC dimer but not other HLA-class I stained LILRB5-transfected 293T cells. B27 dimer binding to LILRB5 was blocked with the class I heavy chain antibody HC10 and anti-LILRB5 antisera. B27 dimers also bound to LILRB5 on peripheral monocytes. HLA-B7 and B27 heavy chains co-immunoprecipitated with LILRB5 in transduced B and rat basophil RBL cell lines.Our findings show that class I free heavy chains are ligands for LILRB5. The unique binding specificity of LILRB5 for HLA-class I heavy chains probably results from differences in the D1 and D2 immunoglobulin-like binding domains which are distinct from other LILR which bind to β2m-associated HLA-class I.

  19. Identification of seven novel HLA class I alleles in New Zealand.

    Science.gov (United States)

    Lamb, G; Choi, K-L; Selwyn, C; Wheeler, A; Hammond, L; Morgan, J; Dunn, P P J

    2015-10-01

    Seven new HLA class I alleles have been identified in the New Zealand population in the process of routine HLA typing and they are described here. Unusual bead positivity in Luminex typing identified potential new alleles in a bone marrow registry donor (B*40:285) and two HIV patients prior to abacavir prescription (B*14:02:09, B*41:29). In addition, four new class I alleles were identified through class I sequencing-based typing (SBT) outside of exons 2 and 3. One mutation was identified in exon 4 (new allele C*12:125) and three have been found in exon 5, an exon rarely sequenced. Two stem cell transplant recipients (B*07:02:45, C*03:279) had novel mutations in exon 5 and one was found in exon 5 of a potentially matched unrelated donor from DKMS, previously thought to be B*40:02:01 (B*40:303). PMID:26212036

  20. Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

    DEFF Research Database (Denmark)

    McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany; Remesh, Soumya G.; Kaever, Thomas; Bardet, Wilfried; Jackson, Kenneth; McLeod, Rima; Sette, Alessandro; Nielsen, Morten; Zajonc, Dirk M.; Blader, Ira J.; Peters, Bjoern; Hildebrand, William

    2016-01-01

    HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected...

  1. HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6

    DEFF Research Database (Denmark)

    Ødum, Niels; Milman, N; Jakobsen, B K;

    1991-01-01

    The distribution of HLA class II (DR, DQ, and DP) antigens was studied in 41 patients with symptomatic sarcoidosis (SA) and ethnically matched healthy controls. HLA-DR, -DQw1 and -DQw3 typings were performed with alloantisera in the conventional microcytotoxic test, whereas -DP typings were done...

  2. HLA class I haplotypes and progression of primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Fábio Zenha

    2011-04-01

    Full Text Available PURPOSE: To verify if patients with primary open-angle glaucoma with HLA class I haplotypes (A9-B12, A2-B40, A1-B8 associated with this disease may have a greater rate of progression than patients who do not present these haplotypes. METHODS: Anatomical and functional glaucoma evaluation (cup-to-disc ratio and visual field of 25 patients (six of them with one of the haplotypes associated with glaucoma followed at the Glaucoma Outpatient Clinic of the University Hospital, Ribeirão Preto School of Medicine, São Paulo University (HCFMRP-USP for ten years after typing of their HLA antigens in order to compare with their previous condition. RESULTS: A greater increase of the cup-to-disc ratio was observed in patients with HLA haplotypes associated with primary open-angle glaucoma predisposition. However, no significant differences in functional damage progression or in retinal nerve fibers loss were detected between them and other patients with glaucoma. CONCLUSION: The present results indicate an association of class I HLA haplotypes with progression of anatomic alterations of the optic nerve head in glaucomatous patients.

  3. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    International Nuclear Information System (INIS)

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2PQPELPYPQ diffracted to 3.9 Å, while the HLA-DQ8EGSFQPSQE crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4+ T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported

  4. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

    2007-12-01

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

  5. Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes

    NARCIS (Netherlands)

    M.M. van Luijn; M.E.D. Chamuleau; M.E. Ressing; E.J. Wiertz; S. Ostrand-Rosenberg; Y. Souwer; A. Zevenbergen; G.J. Ossenkoppele; A.A. van de Loosdrecht; S.M. Ham

    2010-01-01

    During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA cl

  6. Mixed enzyme-linked immunosorbent assay (MELISA) for HLA class I antigen: a plasma membrane marker.

    Science.gov (United States)

    Bjerrum, O W; Borregaard, N

    1990-03-01

    This study introduces a simple, reproducible assay for HLA class I antigen using antibodies against beta 2-microglobulin and the heavy chain on HLA. The sandwich technique was named mixed enzyme-linked immunosorbent assay (MELISA), and was designed for identification of plasma membranes in neutrophil subcellular fractions. The subcellular localization of HLA was identical to that of other plasma membrane markers, [3H]concanavalin A and detergent-independent alkaline phosphatase, and was unchanged by stimulation of cells by weak and strong secretagogues. In addition to the presence as part of the HLA complex in the plasma membrane uncomplexed beta 2-microglobulin is present in the specific granules of neutrophils. However, the release of beta 2-microglobulin from intact neutrophils stimulated with formyl-methionylleucylphenylalanine was much higher than could be explained by exocytosis of specific granules. Subcellular fractionation studies demonstrated that beta 2-microglobulin is localized in fractions characterized by latent alkaline phosphatase and released from this novel secretory compartment in response to stimulation with formyl-methionylleucylphenylalanine. PMID:2181625

  7. HLA Class II Antibody Activation of Endothelial Cells Promotes Th17 and Disrupts Regulatory T Lymphocyte Expansion.

    Science.gov (United States)

    Lion, J; Taflin, C; Cross, A R; Robledo-Sarmiento, M; Mariotto, E; Savenay, A; Carmagnat, M; Suberbielle, C; Charron, D; Haziot, A; Glotz, D; Mooney, N

    2016-05-01

    Kidney transplantation is the most successful treatment option for patients with end-stage renal disease, and chronic antibody-mediated rejection is the principal cause of allograft loss. Predictive factors for chronic rejection include high levels of HLA alloantibodies (particularly HLA class II) and activation of graft endothelial cells (ECs). The mechanistic basis for this association is unresolved. We used an experimental model of HLA-DR antibody stimulation of microvascular ECs to examine the mechanisms underlying the association between HLA class II antibodies, EC activation and allograft damage. Activation of ECs with the F(Ab')2 fragment of HLA-DR antibody led to phosphorylation of Akt, ERK and MEK and increased IL-6 production by ECs cocultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an Akt-dependent manner. We previously showed that HLA-DR-expressing ECs induce polarization of Th17 and FoxP3(bright) regulatory T cell (Treg) subsets. Preactivation of ECs with anti-HLA-DR antibody redirected EC allogenicity toward a proinflammatory response by decreasing amplification of functional Treg and by further increasing IL-6-dependent Th17 expansion. Alloimmunized patient serum containing relevant HLA-DR alloantibodies selectively bound and increased EC secretion of IL-6 in cocultures with PBMCs. These data contribute to understanding of potential mechanisms of antibody-mediated endothelial damage independent of complement activation and FcR-expressing effector cells. PMID:26614587

  8. Superantigen and HLA-DR ligation induce phospholipase-C gamma 1 activation in class II+ T cells

    DEFF Research Database (Denmark)

    Kanner, S B; Odum, Niels; Grosmaire, L;

    1992-01-01

    Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA-DR) expressed on both APC and activated human T cells, and simultaneously bind to certain V beta chains of the TCR. In this report, we compared early T cell signaling events in human alloantigen-stimulated T cells when...... activated by HLA-DR ligation through antibody cross-linking or by direct enterotoxin superantigen binding. Both types of stimuli induced tyrosine phosphorylation of phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an increase in intracellular calcium concentration; however......, superantigen-induced signaling was stronger than class II ligation alone. Antibody-mediated ligation of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased calcium mobilization, consistent with a mechanism of superantigen activity through a combination of class II and CD3/Ti signals. In...

  9. Lack of association between alopecia areata and HLA class I and II in a southeastern Brazilian population*

    Science.gov (United States)

    Barbosa, Ângela Marques; Prestes-Carneiro, Luiz Euribel; Sobral, Aldri Roberta Sodoschi; Sakiyama, Marcelo Jun; Lemos, Bruna Cerávolo; de Abreu, Marilda Aparecida Milanez Morgado; Martos, Luciana Leite Crivelin; Moliterno, Ricardo Alberto

    2016-01-01

    Background Alopecia areata (AA) is a common disorder of unknown etiology that affects approximately 0.7% to 3.8% of patients among the general population. Currently, genetic and autoimmune factors are emphasized as etiopathogenic. Studies linking Human Leukocyte Antigens (HLA) to AA have suggested that immunogenetic factors may play a role in the disease's onset/development. Objectives To investigate an association between AA and HLA class I/II in white Brazilians. Methods: Patients and control groups comprised 33 and 112 individuals, respectively. DNA extraction was performed by column method with BioPur kit. Allele's classification was undertaken using the PCR-SSO technique. HLA frequencies were obtained through direct counting and subjected to comparison by means of the chi-square test. Results Most patients were aged over 16, with no familial history, and developed partial AA, with no recurrent episodes. Patients showed a higher frequency of HLA-B*40, HLA-B*45, HLA-B*53 and HLA-C*04 compared with controls, although P was not significant after Bonferroni correction. Regarding HLA class II, only HLA-DRB1*07 revealed statistical significance; nevertheless, it featured more prominently in controls than patients (P=0.04; Pc=0.52; OR=0.29; 95%; CI=0.07 to 1.25). P was not significant after Bonferroni correction. Conclusions The development of AA does not seem to be associated with HLA in white Brazilians, nor with susceptibility or resistance. The studies were carried out in populations with little or no miscegenation, unlike the Brazilian population in general, which could explain the inconsistency found.

  10. HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc Patients.

    Directory of Open Access Journals (Sweden)

    Tatiana S Rodriguez-Reyna

    Full Text Available Human leukocyte antigen (HLA polymorphism studies in Systemic Sclerosis (SSc have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications.We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population.Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02, and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients.This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as

  11. "HLA Class II Allele and Haplotype Frequencies in Iranian Patients with Acute Myelogenous Leukemia and Control Group "

    Directory of Open Access Journals (Sweden)

    Abdolfattah Sarafnejad

    2006-09-01

    Full Text Available Previous studies have demonstrated some significant differences in HLA allele frequencies in leukemic patients and normal subjects. We have analyzed HLA class II alleles and haplotypes in 60 Iranian patients with acute myelogenous leukemia (AML and 180 unrelated normal subjects. Blood samples were collected after obtaining informed consents. From the patients and control DNA extraction and HLA typing were performed using PCR-SSP method. Significant positive association with the disease was found for HLA-DRB1*11 allele (35% vs. 24.7%, p=0.033. Two alleles including HLA-DRB4 and –DQB1*0303 were found to be significantly decreased in patients compared to controls. Regarding haplotype analysis, no significant association was found between case and control groups. It is suggested that HLA-DRB1*11 allele plays as a presumptive predisposing factor while the HLA-DRB4 and –DQB1*0303 alleles are suggested as protective genetic factors against acute myelogenous leukemia. Larger studies are needed to confirm and establish the role of these associations with acute myelogenous leukemia.

  12. Lack of association between parenchymal neurocysticercosis and HLA Class I and Class II antigens

    Directory of Open Access Journals (Sweden)

    Eni Picchioni Bompeixe

    1999-03-01

    Full Text Available Neurocysticercosis, caused by encysted larvae of the tapeworm Taenia solium, is the most common infection of the central nervous system and a major public health problem in many countries. Prevalence in the region of Curitiba, located in the southern Brazilian State of Paraná, is one of the highest in the world. The genetics of host susceptibility to neurocysticercosis (NCC is still obscure. To investigate if major histocompatibility complex (MHC genes influence individual susceptibility to NCC, we performed a case-control association analysis. Fifty-two Caucasoid patients and 149 matched controls were typed for antigens of the HLA-A, B, C, DR and DQ loci. All patients had computerized tomography and clinical features compatible with parenchymal NCC. Indirect immunofluorescence of cerebrospinal fluid showed that 19 (37% of the patients presented anti-cysticercus antibodies at titers ³ 1:10. Frequencies of HLA specificities in the whole group of patients and in the subgroup with antibodies in cerebrospinal fluid were compared to those of the control group. No significant difference was found. These results do not support the hypothesis of HLA gene participation in susceptibility to parenchymal neurocysticercosis.A neurocisticercose, causada pelo cisticerco, a larva do cestóide Taenia solium, é a infecção mais comum do sistema nervoso central e constitui importante problema de saúde pública em muitos países. A sua prevalência na região de Curitiba, localizada no Estado do Paraná, foi estimada em 9%, situando-se entre as mais elevadas do mundo. Os aspectos genéticos de suscetibilidade à neurocisticercose (NCC ainda são pouco conhecidos. Com o objetivo de investigar se genes do MHC influenciam a suscetibilidade individual à NCC, realizamos uma análise de associação caso-controle. Cinqüenta e dois pacientes caucasóides e 149 indivíduos-controle pareados foram tipados para antígenos dos locos HLA-A, B, C, DR e DQ. Todos os

  13. Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines

    International Nuclear Information System (INIS)

    The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines. Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan® Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells. Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway. We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence

  14. Regressing and progressing metastatic lesions: resistance to immunotherapy is predetermined by irreversible HLA class I antigen alterations.

    Science.gov (United States)

    Aptsiauri, Natalia; Carretero, Rafael; Garcia-Lora, Angel; Real, Luis M; Cabrera, Teresa; Garrido, Federico

    2008-11-01

    Despite the significant efforts to enhance immune reactivity against malignancies the clinical effect of anti-tumor vaccines and cancer immunotherapy is still below expectations. Understanding of the possible causes of such poor clinical outcome has become very important for improvement of the existing cancer treatment modalities. In particular, the critical role of HLA class I antigens in the success of T cell based immunotherapy has led to a growing interest in investigating the expression and function of these molecules in metastatic cancer progression and, especially in response to immunotherapy. In this report, we illustrate that two types of metastatic lesions are commonly generated in response to immunotherapy according to the pattern of HLA class I expression. We found that metastatic lesions, that progress after immunotherapy have low level of HLA class I antigens, while the regressing lesions demonstrate significant upregulation of these molecules. Presumably, immunotherapy changes tumor microenvironment and creates an additional immune selection pressure on tumor cells. As a result, two subtypes of metastatic lesions arise from pre-existing malignant cells: (a) regressors, with upregulated HLA class I expression after therapy, and (b) progressors with resistance to immunotherapy and with low level of HLA class I. Tumor cells with reversible defects (soft lesions) respond to therapy by upregulation of HLA class I expression and regress, while tumor cells with structural irreversible defects (hard lesions) demonstrate resistance to immunostimulation, fail to upregulate HLA class I antigens and eventually progress. These two types of metastases appear independently of type of the immunotherapy used, either non-specific immunomodulators (cytokines or BCG) or autologous tumor vaccination. Similarly, we also detected two types of metastatic colonies in a mouse fibrosarcoma model after in vitro treatment with IFN-gamma. One type of metastases characterized by

  15. Analysis of HLA class I-II haplotype frequency and segregation in a cohort of patients with advanced stage ovarian cancer.

    Science.gov (United States)

    Gamzatova, Z; Villabona, L; van der Zanden, H; Haasnoot, G W; Andersson, E; Kiessling, R; Seliger, B; Kanter, L; Dalianis, T; Bergfeldt, K; Masucci, G V

    2007-09-01

    In solid tumors, human leucocyte antigen (HLA)-A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA-A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA-A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III-IV was found. Thirty-two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA-A, HLA-B, HLA-Cw, and HLA-DRB1 loci by the polymerase chain reaction/sequence-specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA-A1 and HLA-A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA-A3 was decreased. HLA-A2 homozygotes were twofold higher in patients. The A2-B8 haplotype was significantly increased (corrected P value). A2-B5, A2-B15, A2-DRB1*03, A2-DRB1*04, A2-B15-Cw3, and A2-B8-DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non-corrected analysis. HLA-B15 and HLA-Cw3 were only present in HLA-A2-positive patients showing that the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations. PMID:17661908

  16. Pan-specific MHC class I predictors: A benchmark of HLA class I pan-specific prediction methods

    DEFF Research Database (Denmark)

    Zhang, Hao; Lundegaard, Claus; Nielsen, Morten

    2009-01-01

    MHCpan methods. Conclusions: The benchmark demonstrated that pan-specific methods do provide accurate predictions also for previously uncharacterized MHC molecules. The NetMHCpan method trained to predict actual binding affinities was consistently top ranking both on quantitative (affinity) and binary (ligand......) data. However, the KISS method trained to predict binary data was one of the best performing when benchmarked on binary data. Finally, a consensus method integrating predictions from the two best-performing methods was shown to improve the prediction accuracy. Associate Editor: Prof. Thomas Lengauer....... emerging pathogens. Methods have recently been published that are able to predict peptide binding to any human MHC class I molecule. In contrast to conventional allele-specific methods, these methods do allow for extrapolation to un-characterized MHC molecules. These pan-specific HLA predictors have not...

  17. HLA class II antigens and haplotypes associated with susceptibility of leukemias and myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Genetical and environmental factors play an interactive role in the development of acute and chronic leukemias. HLA antigens have been considered as possible genetic risk factors. The aim of this work was to investigate a possible association between HLA class II polymorphisms and leukemias and myelodysplastic syndrome. In the present study we investigated HLA class II antigens, DR/DQ and DR51/DR52/DR53 haplotypes in 100 patients: 7 suffering from myelodysplastic syndrome (MDS,37 from acute lymphoblastic leukemia(ALL,32 from acute myeloid leukemia (AML and 24 from chronic myeloid leukemia(CML. A panel of 210 healthy unrelated individuals of the same origin, from Vojvodina, served as controls. HLA phenotyping was performed by two color fluorescence method. In patients suffering from MDS was found a positive association with DR7(RR=2.598,EF=0.175 and DQ7(3(RR=4.419, EF=0.632, while negative association was found for DR15(2(RR=0.405, PF=0.172 and DQ6(1 (RR=0.889, PF=0,936.Positive association was found in the group of patients with ALL for DR7(RR=2.391,EF=0.688 and DQ2(RR=1.62, EF=0.15,while negative association was found with DQ5(1(RR=0.075, PF=0.324. In the group of patients with AML, there were positive associations with DR11(5(RR=1.732,EF=0.211,DQ2(RR= 1.594, EF=0.151 and DQ7(3 (RR=2.547,EF=0.266,while possible protective antigen was DQ5(1 (RR=0.107,RF=0.701. Higher RR than 1 and EF>0.15, in patients suffering from CML was found for DQ6(1(RR=1.661,EF=0.232, while negative association was found for DR4 (RR=0.182,PF=0.155.Possible protective haplotype in this study was DR3DQ8(3 for patients suffering from AML(RR=0.007, PF=0.501.The distribution of DR53-DR53 haplotypes showed significant difference in male patients with ALL(6% vs 0.09%, while DR52-DR52 haplotype was significantly less frequent in male patients with CML (4% vs 20.47% and female patients with MDS (1% vs 18.57%, respectively, in comparison to controls. We deduced that DR7 antigen in

  18. Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

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    Paola Cruz-Tapias

    2012-01-01

    Full Text Available The prevalence and genetic susceptibility of autoimmune diseases (ADs may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53 was found to be a risk factor for systemic lupus erythematosus (SLE, Sjögren's syndrome (SS, and type 1 diabetes mellitus (T1D. DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05 influences autoimmune hepatitis (AIH, rheumatoid arthritis (RA, and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42 is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

  19. Molecular typing of HLA class II antigens in a São Paulo population

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    Goldberg A.C.

    1998-01-01

    Full Text Available In the present paper we show data obtained from a normal population with a racially mixed profile typical of the city of São Paulo, State of São Paulo. Data were generated with polymerase chain reaction using sequence specific primers (PCR-SSP for HLA-DRB and polymerase chain reaction followed by hybridization with sequence specific oligonucleotide probes (PCR-SSO for HLA-DQA1 and HLA-DQB1 loci. HLA-DRB, DQA1, DQB1 and haplotype frequencies as well as common linkage disequilibria were found. This population was also shown to be in genetic equilibrium according to the Hardy-Weinberg law. HLA-DR typing of a normal sample from the city of Porto Velho, State of Rondonia, highlighted the importance of different sets of HLA profiles found in other regions of the country. This database provides essential information for screening studies of disease associations, forensic analyses and transplants.

  20. The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    2016-08-01

    Full Text Available ABSTRACT Objective To study the HLA of class 1and 2 in a multiple sclerosis (MS population to verify the susceptibility for the disease in the Southern Brazil. Methods We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. Results We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Conclusions Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

  1. Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion

    DEFF Research Database (Denmark)

    Odum, Niels; Yoshizumi, H; Okamoto, Y;

    1992-01-01

    Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was...... antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was......, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through...

  2. The Expression of Non-Classical HLA Class I Molecules (HLA-Gand HLA-E)in Human Tumor Cell Lines and the Regulatory Effect of IFN-γ%非经典hla Ⅰ类分子(hla-g和hla-e)在人肿瘤细胞系的表达及ifn-γ的调节作用

    Institute of Scientific and Technical Information of China (English)

    张彩; 田志刚; 魏海明; 冯进波; 许晓群; 张建华; 孙汭

    2001-01-01

    目的:探讨非经典hla Ⅰ类分子在人肿瘤细胞系的表达及ifn-γ的调节作用。方法:用rt-pcr法检测12种肿瘤细胞系和人脑胶质瘤组织及妊娠妇女滋养层组织标本hla-g和hla-e mrna的表达。结果:人脑胶质瘤组织及妊娠妇女滋养层组织均有hla-g和hla-e mrna的表达;12株肿瘤细胞中仅人t细胞淋巴瘤karpas存在hla-g3的mrna表达,经ifn-γ处理后,karpas出现hla-g1/g5和hla-g2/g4的表达,宫颈癌hela细胞、黑色素瘤m21细胞和膀胱癌t24细胞出现hla-g3 mrna的表达;12株肿瘤细胞中有9株表达hla-e mrna。结论:肿瘤存在hla-g和hla-e mrna的表达,ifn-γ可促进hla-g mrna的表达。肿瘤细胞hla-g和hla-e的表达可能是肿瘤逃避免疫系统监视的机制之一。

  3. Susceptible and protective HLA class 1 alleles against dengue fever and dengue hemorrhagic fever patients in a Malaysian population.

    Directory of Open Access Journals (Sweden)

    Ramapraba Appanna

    Full Text Available BACKGROUND: The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B of DENV infected patients against healthy individuals in Malaysia. METHODOLOGY/PRINCIPAL FINDINGS: This study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P = 0.042, Pc = 1.008 allele and a significant decrease for A*03 (P = 0.015, Pc = 0.18, OR = 5.23, 95% CI = 1.19-23.02 and B*18 (P = 0.017, Pc = 0.408 alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P = 0.049, Pc = 1.176, OR = 0.18, 95% CI = 0.03-0.90 was present at a significantly higher frequency in this population while allele HLA-B*18 (P = 0.024, Pc = 0.576 was seen to be negatively associated with DHF. CONCLUSIONS/SIGNIFICANCE: These are the first findings on genetic polymorphisms in our population and we conclude that: (1 In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2 In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine.

  4. Susceptible and Protective HLA Class 1 Alleles against Dengue Fever and Dengue Hemorrhagic Fever Patients in a Malaysian Population

    OpenAIRE

    Appanna, Ramapraba; Ponnampalavanar, Sasheela; Lum Chai See, Lucy; Sekaran, Shamala Devi

    2010-01-01

    Background The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV) infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B) of DENV infected patients against healthy individuals in Malaysia. Methodology/Principal Findings This study was carried out with 92 dengue disease patients and 95 healthy cont...

  5. Allele-Independent Turnover of Human Leukocyte Antigen (HLA) Class Ia Molecules.

    Science.gov (United States)

    Prevosto, Claudia; Usmani, M Farooq; McDonald, Sarah; Gumienny, Aleksandra M; Key, Tim; Goodman, Reyna S; Gaston, J S Hill; Deery, Michael J; Busch, Robert

    2016-01-01

    Major histocompatibility complex class I (MHCI) glycoproteins present cytosolic peptides to CD8+ T cells and regulate NK cell activity. Their heavy chains (HC) are expressed from up to three MHC gene loci (human leukocyte antigen [HLA]-A, -B, and -C in humans), whose extensive polymorphism maps predominantly to the antigen-binding groove, diversifying the bound peptide repertoire. Codominant expression of MHCI alleles is thus functionally critical, but how it is regulated is not fully understood. Here, we have examined the effect of polymorphism on the turnover rates of MHCI molecules in cell lines with functional MHCI peptide loading pathways and in monocyte-derived dendritic cells (MoDCs). Proteins were labeled biosynthetically with heavy water (2H2O), folded MHCI molecules immunoprecipitated, and tryptic digests analysed by mass spectrometry. MHCI-derived peptides were assigned to specific alleles and isotypes, and turnover rates quantified by 2H incorporation, after correcting for cell growth. MHCI turnover half-lives ranged from undetectable to a few hours, depending on cell type, activation state, donor, and MHCI isotype. However, in all settings, the turnover half-lives of alleles of the same isotype were similar. Thus, MHCI protein turnover rates appear to be allele-independent in normal human cells. We propose that this is an important feature enabling the normal function and codominant expression of MHCI alleles. PMID:27529174

  6. HLA class II genes in chronic hepatitis C virus-infection and associated immunological disorders.

    Science.gov (United States)

    Congia, M; Clemente, M G; Dessi, C; Cucca, F; Mazzoleni, A P; Frau, F; Lampis, R; Cao, A; Lai, M E; De Virgiliis, S

    1996-12-01

    To investigate the factors that may confer susceptibility or protection to hepatitis C virus (HCV) infection and to HCV-associated immunological disorders, we designed two studies on 420 Sardinian transfusion-dependent thalassemia patients followed in our department in Cagliari since 1974. The first one was an epidemiological survey aimed to evaluate the prevalence of HCV infection and HCV-associated immunological disorders. In the second study, the distribution of different HLA class II genes was examined by DNA analysis in 116 HCV positive patients, 30 HCV negative patients, and 606 healthy controls. Three hundred fourteen patients became infected with HCV (74.7%) after 5.6 +/- 2.8 years of regular transfusion program. Mixed cryoglobulinemia, purpura, arthritis, proteinuria, decreased complement levels, rheumatoid factor and anti-GOR, smooth muscle antibody (SMA), anti-nuclear antibody (ANA), and liver, kidney microsome (LKM) autoantibodies were significantly more represented in HCV positive patients than in negative ones (P patients who despite 10.3 +/- 2.2 years in a regular blood transfusion program did not show any evidence of HCV infection (Pc < .0092). Our results represent clear evidence for a relationship between HCV infection and immune extrahepatic abnormalities. A gene(s) located in the human major histocompatibility complex (MHC) region may play an important role in conferring protection against HCV infection. PMID:8938157

  7. HLA-DMA polymorphisms differentially affect MHC class II peptide loading.

    Science.gov (United States)

    Álvaro-Benito, Miguel; Wieczorek, Marek; Sticht, Jana; Kipar, Claudia; Freund, Christian

    2015-01-15

    During the adaptive immune response, MHCII proteins display antigenic peptides on the cell surface of APCs for CD4(+) T cell surveillance. HLA-DM, a nonclassical MHCII protein, acts as a peptide exchange catalyst for MHCII, editing the peptide repertoire. Although they map to the same gene locus, MHCII proteins exhibit a high degree of polymorphism, whereas only low variability has been observed for HLA-DM. As HLA-DM activity directly favors immunodominant peptide presentation, polymorphisms in HLA-DM (DMA or DMB chain) might well be a contributing risk factor for autoimmunity and immune disorders. Our systematic comparison of DMA*0103/DMB*0101 (DMA-G155A and DMA-R184H) with DMA*0101/DMB*0101 in terms of catalyzed peptide exchange and dissociation, as well as direct interaction with several HLA-DR/peptide complexes, reveals an attenuated catalytic activity of DMA*0103/DMB*0101. The G155A substitution dominates the catalytic behavior of DMA*0103/DMB*0101 by decreasing peptide release velocity. Preloaded peptide-MHCII complexes exhibit ∼2-fold increase in half-life in the presence of DMA*0103/DMB*0101 when compared with DMA*0101/DMB*0101. We show that this effect leads to a greater persistence of autoimmunity-related Ags in the presence of high-affinity competitor peptide. Our study therefore reveals that HLA-DM polymorphic residues have a considerable impact on HLA-DM catalytic activity. PMID:25505276

  8. Evidence for a new HLA class II determinant present on cells from HLA-DR1 and/or -DR4 individuals.

    Science.gov (United States)

    Lepage, V; Alcalay, D; Douay, C; Mallet, C; Loiseau, P; Degos, L; Colombani, M; Colombani, J

    1985-02-01

    Evidence for a new HLA class II specificity is presented. It is recognized by LE serum, which reacts with most DR1 and/or DR4 individuals (r = 0.86). Its frequency in the French population is 0.33. Absorption-elution experiments showed that the serum reactivity was not due to a mixture of anti-DR1 and anti-DR4 antibodies, but to a single antibody population which could be absorbed on and eluted from both DR1(+) or DR4(+) cells. LE specificity seemed to be expressed on DR but not on DQ molecules since the serum reacted with and could be absorbed by DR+,DQw- cells; it did not react with a DR-,DQw+ mutant cell, but did react with the DR+,DQw+ parental cell. The relationship between LE specificity and MC1 and Te23 specificities remains to be determined. PMID:2581334

  9. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves; Valsesia, Armand; Lammers, Gert J; Donjacour, Claire E H M; Iranzo, Alex; Santamaria, Joan; Peraita Adrados, Rosa; Vicario, José L; Overeem, Sebastiaan; Arnulf, Isabelle; Theodorou, Ioannis; Jennum, Poul; Knudsen, Stine; Bassetti, Claudio; Mathis, Johannes; Lecendreux, Michel; Mayer, Geert; Geisler, Peter; Benetó, Antonio; Petit, Brice; Pfister, Corinne; Bürki, Julie Vienne; Didelot, Gérard; Billiard, Michel; Ercilla, Guadalupe; Verduijn, Willem; Claas, Frans H J; Vollenweider, Peter; Vollenwider, Peter; Waeber, Gerard; Waterworth, Dawn M; Mooser, Vincent; Heinzer, Raphaël; Beckmann, Jacques S; Bergmann, Sven; Tafti, Mehdi

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing...... narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1...... ratio = 0.02; P <6 x 10(-14)). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility....

  10. High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients' sera.

    Science.gov (United States)

    Ritz, Danilo; Gloger, Andreas; Weide, Benjamin; Garbe, Claus; Neri, Dario; Fugmann, Tim

    2016-05-01

    The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high-confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan-reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies. PMID:26992070

  11. Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Ahmed A Mostafa

    Full Text Available The coordinate regulation of HLA class II (HLA-II is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E₂ and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER⁻ and ER⁺ breast cancer cell lines, we showed that E₂ attenuated HLA-DR in two ER⁺ lines (MCF-7 and BT-474, but not in T47D, while it augmented expression in ER⁻ lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s, we used paired transfectants: ERα⁺ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene and ERα⁻ VC5 (MDA-MB-231 c10A transfected with the empty vector, treated or not with E₂ and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E₂ treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E₂ in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα⁻ breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα⁺ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

  12. Antibodies against a class II HLA-peptide complex raised by active immunization of mice with antigen mimicking peptides

    DEFF Research Database (Denmark)

    Dam-Tuxen, R; Riise, Erik Skjold

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune disease linked to the human leucocyte antigen (HLA) class II genes DRB1*1501, DRB5*0101 and DQB1*0602. T cells reactive towards the DRB1*1501 in complex with various peptides derived from myelin basic protein (MBP), which is the major component of myelin......, have been found in the peripheral blood of MS patients. These autoreactive T cells are believed to play a role in the pathogenesis of MS. In this article, antibodies against the HLA complex DR2b (DRA1*0101/DRB1*1501) in complex with the MBP-derived peptide MBP(85-99) have been generated by immunization...

  13. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Karanikiotis, C. [424 Army General Hospital, Thessaloniki (Greece); Daniilidis, M.; Karyotis, N.; Nikolaou, A. [AHEPA Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece); Bakogiannis, C. [Hygeia Hospital, Athens (Greece); Economopoulos, T. [' Attikon' Univ. Hospital, Athens (Greece); Murray, S. [Metropolitan Hospital, Athens (Greece); Papamichael, D. [Bank of Cyprus Oncology Center, Nicosia, Cyprus (Greece); Samantas, E. [' Agii Anargiri' Cancer Hospital, Athens (Greece); Skoura, L. [' Hippokration' Hospital, Thessaloniki (Greece); Tselis, N.; Zamboglou, N. [Dept. of Radiotherapy, Offenbach Hospital (Germany); Fountzilas, G. [' Papageorgiou' Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece)

    2008-06-15

    Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

  14. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

  15. 瘢痕疙瘩与HLA-Ⅱ类基因相关性研究%Study on correlation between HLA class Ⅱ gene and keloids

    Institute of Scientific and Technical Information of China (English)

    陈东明; 李生; 鲍卫汉

    2004-01-01

    目的:探讨免疫遗传学因素在瘢痕疙瘩发病机制中的作用.方法:用聚合酶链反应-序列特异性引物(PCR-SSP)技术对50例瘢痕疙瘩患者进行HLA-Ⅱ类基因分型,并以100例正常人的HLA-Ⅱ类基因为对照.结果:瘢痕疙瘩组HLA-DQ5抗原频率(30%)明显高于对照组(14%),相对危险率(RR)=2.63;HLA-DR17和HLA-DQ8抗原频率(2%)明显低于对照组(14%,15%),RR=0.13,0.12.结论:瘢痕疙瘩与HLA-DQ5基因呈正相关,与HLA-DR17和HLA-DQ8基因呈负相关.HLA-DQ5、HLA-DR17和HLA-DQ8基因可能是瘢痕疙瘩患者易感的单倍型.

  16. Quantificação de antígenos HLA classe I solúveis pela técnica de ELISA - DOI: 10.4025/actascihealthsci.v31i2.6758 Quantification of soluble HLA class I antigens by ELISA assay- DOI: 10.4025/actascihealthsci.v31i2.6758

    Directory of Open Access Journals (Sweden)

    Marciele Coan Boian

    2009-09-01

    Full Text Available As moléculas HLA (Human Leucocyte Antigens são consideradas, principalmente, estruturas de superfície celular envolvidas em uma variedade de reações imunes associadas com transplante, infecções e doenças autoimunes. Os antígenos HLA também podem ser encontrados, em forma solúvel, no soro e em diferentes fluidos do organismo humano. Este trabalho teve como objetivo desenvolver a técnica imunoenzimática (ELISA para quantificar os níveis séricos de antígenos HLA classe I, específicos e totais, em indivíduos normais e em pacientes renais. A técnica de ELISA foi desenvolvida para demonstrar a presença, no soro, de antígenos HLA classe I totais (sHLA-I e as especificidades HLA-A2 (sHLA-A2 e HLA-B7 (sHLA-B7. Oitenta e oito amostras de soro foram envolvidas neste estudo, sendo 61 amostras provenientes de indivíduos sadios cadastrados no Hemocentro Regional de Maringá, Estado do Paraná, e 27 pacientes renais, provenientes dos centros de diálise da cidade de Maringá, Estado do Paraná. As concentrações médias de sHLA para as especificidades -A2 e -B7, detectadas somente em indivíduos sadios, foram 504.06 ng mL-1 ± 142.10 e 427.33 ng mL-1 ± 140.73, respectivamente. Resultados preliminares mostraram que sHLA-I, em indivíduos sadios, foi de 253,77 ng mL-1 e, em indivíduos renais em diálise, de 381,67 ng mL-1. A técnica de ELISA para detecção de antígenos HLA solúveis poderá ser útil em estudos comparativos, em diferentes populações saudáveis, diferentes patologias e no monitoramento das rejeições em transplantes.HLA (Human Leucocyte Antigens molecules are regarded mainly as cell surface structures involved in several immune reactions associated with transplants, infections and auto-immune diseases. HLA antigens can be also found in soluble form in serum and in different fluids of the human body. The aim of this work was to develop the immunoenzymatic assay (ELISA to quantify serum levels of specific and total

  17. Association between HLA class I and class II alleles and the outcome of West Nile virus infection: an exploratory study.

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    Marion C Lanteri

    Full Text Available BACKGROUND: West Nile virus (WNV infection is asymptomatic in most individuals, with a minority developing symptoms ranging from WNV fever to serious neuroinvasive disease. This study investigated the impact of host HLA on the outcome of WNV disease. METHODS: A cohort of 210 non-Hispanic mostly white WNV(+ subjects from Canada and the U.S. were typed for HLA-A, B, C, DP, DQ, and DR. The study subjects were divided into three WNV infection outcome groups: asymptomatic (AS, symptomatic (S, and neuroinvasive disease (ND. Allele frequency distribution was compared pair-wise between the AS, S, and ND groups using χ2 and Fisher's exact tests and P values were corrected for multiple comparisons (Pc. Allele frequencies were compared between the groups and the North American population (NA used as a control group. Logistic regression analysis was used to evaluate the potential synergistic effect of age and HLA allele phenotype on disease outcome. RESULTS: The alleles HLA-A*68, C*08 and DQB*05 were more frequently associated with severe outcomes (ND vs. AS, P(A*68 = 0.013/Pc = 0.26, P(C*08 = 0.0075/Pc = 0.064, and P(DQB1*05 = 0.029/Pc = 0.68, However the apparent DQB1*05 association was driven by age. The alleles HLA-B*40 and C*03 were more frequently associated with asymptomatic outcome (AS vs. S, P(B*40 = 0.021/Pc = 0.58 and AS vs. ND P(C*03 = 0.039/Pc = 0.64 and their frequencies were lower within WNV(+ subjects with neuroinvasive disease than within the North American population (NA vs. S, P(B*40 = 0.029 and NA vs. ND, P(C*03 = 0.032. CONCLUSIONS: Host HLA may be associated with the outcome of WNV disease; HLA-A*68 and C*08 might function as "susceptible" alleles, whereas HLA-B*40 and C*03 might function as "protective" alleles.

  18. Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy

    DEFF Research Database (Denmark)

    Nielsen, Henriette Svarre; Steffensen, Rudi; Varming, Kim;

    2009-01-01

    Healthy females, pregnant with a boy, generate immune responses against male-specific minor histocompatibility (HY) antigens. The clinical importance of these responses is evident in stem cell transplantation. Birth of a boy prior to a series of miscarriages reduces the chance of a subsequent live...... birth. This study explores the putative impact of known HY-presenting HLA alleles on future pregnancy outcome in women with at least three consecutive miscarriages following a birth [secondary recurrent miscarriage (SRM)]. HLA-A, -B, -DRB1, DRB3-5 and DQB1 genotyping was performed in 358 SRM patients...... and in 203 of their children born prior to the miscarriages. The subsequent live birth in women with boys prior to the miscarriages compared with girls is lower in women with HY-restricting HLA class II alleles [odds ratio (OR): 0.17 (0.1-0.4), P = 0.0001]. One HY-restricting HLA class II allele in...

  19. Global stability analysis on a class of cellular neural networks

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The existence, uniqueness, globally exponential stability andspeed of exponential convergence for a class of cellular neural networks are investigated. The existence of a unique equilibrium is proved under very concise conditions, and theorems for estimating the global convergence speed approaching the equilibrium and criteria for its globally exponential stability are derived, Considering synapse time delay, by constructing appropriate Lyapunov functional, the existence of a unique equilibrium and its global stability for the delayed network are also proved. The results, which do not require the cloning template to be symmetric, are easy to use in network design.

  20. HLA Class II Alleles Susceptibility Markers of Type 1 Diabetes Fail to Specify Phenotypes of Ketosis-Prone Diabetes in Adult Tunisian Patients

    Directory of Open Access Journals (Sweden)

    Lilia Laadhar

    2011-01-01

    Full Text Available We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD in a sample of Tunisian patients using the Aβ scheme based on the presence or absence of β-cell autoantibodies (A+ or A− and β-cell functional reserve (β+ or β− and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, β-cell autoimmunity, β-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+β−, 23.3% A−β−, 11.6% A+β+ and 41.9% A−β+. Patients from the group A+β− were significantly younger than those from the group A−β− (P=.002. HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P=.003. These patients also had resistance alleles but they were more frequent in A+β+ than A+β− patients (P=.04. Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.

  1. Estudio de la compatibilidad por métodos serológicos (HLA y celulares (CML en 22 años de trabajo en el Instituto de Hematología e Inmunología Compatibility study by serological (HLA and cellular methods (MLC during 22 years of work at the Institute of Hematology and Immunology

    Directory of Open Access Journals (Sweden)

    Luz M Morera Barrios

    2003-12-01

    Full Text Available Se estudió la histocompatibilidad de los loci ABC y del locus D del sistema principal de histocompatibilidad mediante las técnicas serológicas de microlinfocitotoxicidad en 383 pacientes con diferentes enfermedades hematológicas. Se realizó una comparación por la técnica celular y la reactividad linfocitaria en el cultivo mixto de linfocitos (CML, en 39 de los 145 individuos idénticos para los antígenos HLA, tomados de los estudios familiares realizados en el IHI. Resultaron 29 CML negativos, para el 74,35 %. No se corresponden en el 100 % los estudios serológicos y celulares, ya que no se compatibilizó en todos los casos para los antígenos HLA de clase II, y en ninguno para los antígenos menores de histocompatibilidad, que influyen tanto en los resultados del CML y en las causas de fracaso del trasplante de médula ósea (TMO en individuos idénticos. Esto corrobora la importancia de los estudios de tipificación de biología molecular y antígenos menores de histocompatibilidadCompatibility study by serological (HLA and cellular methods (MLC during 22 years of work at the Institute of Hematology and Immunology The histocompatibility of the loci ABC and of the locus D of the main histocompatibility system was studied by the serological techniques of microlymphocytoxicity in 383 patients with different hematological diseases. A comparison was made in 39 of the 145 identical individuals for the HLA antigens obtained from the family studies conducted at the Institute of Hematology and Immunology by using the cellular technique and the lymphocytary reactivity in the mixed lymphocyte culture (MLC. 29 MLC proved to be negative, accounting for 74.35 %. There was not a 100 % correspondance between the serological and cellular studies, since it was not compatibilized in all cases for class II HLA antigens and in no case for the minor histocompatibility antigens that influence on the results of the MLC and on the causes of the failure of

  2. HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition

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    Azim Hossain

    2011-01-01

    Full Text Available While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity.

  3. HLA class II restricted minor histocompatibility antigens - identification, processing and biology

    OpenAIRE

    Kremer, Anita Natalie

    2014-01-01

    Allogeneic stem cell transplantation is a potentially curative treatment for many hematological malignancies. The beneficial Graft-versus-Leukemia (GvL) effect is thereby mediated by donor-derived T-cells recognizing the malignant cells of the patient as foreign. However, the same T-cells might also target healthy non-hematopoietic cells of the patient such as skin, liver and gut causing a detrimental and sometimes lethal side effect, referred to as Graft-versus-Host disease (GvHD). In HLA-ma...

  4. Identification of a sulfate-bearing molecule associated with HLA class II antigens.

    OpenAIRE

    Sant, A J; Cullen, S E; Schwartz, B D

    1984-01-01

    The human Ia antigens (DR, DS, and SB), determined by genes contained within the HLA complex on chromosome 6, are glycoprotein heterodimers consisting of a Mr approximately equal to 34,000 alpha chain and a Mr approximately equal to 28,000 beta chain. As a result of studies exploring the possibility that alpha or beta (or both) might be sulfated, a unique component of the oligomeric Ia antigen complex was discovered. When anti-Ia immunoprecipitates from Nonidet P-40 lysates of [35S]sulfate-la...

  5. HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis

    OpenAIRE

    1996-01-01

    To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cell...

  6. Sub-classes and evolution stability of Wolfram's classesin the total-rule cellular automata

    Institute of Scientific and Technical Information of China (English)

    YAN Guangwu; TIAN Feng; DONG Yinfeng

    2004-01-01

    In this paper, we propose a concept of sub-classes and its evolution stability for the Wolfram's classes. Firstly, we obtain the sub-classes of the Wolfram's class IV, gene-piece of these sub-classes and their existing circumstance. Secondly, we introduce a new concept, the evolution stability, for the Wolfram's classes and sub-classes of Wolfram's class IV. Lastly, we find that Wolfram's classes I, II, and III have the evolution stability, but sub-classes of the Wolfram's class IV have not the evolution stability for the total rule cellular automata.

  7. Naturally processed measles virus peptide eluted from class II HLA-DRB1*03 recognized by T lymphocytes from human blood

    International Nuclear Information System (INIS)

    This is the first report of the direct identification of a HLA-DRB1*03 measles-derived peptide from measles virus infected EBV-transformed B cells. We purified HLA-DR3-peptide complexes from EBV-B cells infected with measles virus (Edmonston strain) and sequenced the HLA-DR3-peptides by mass spectrometry. A class II peptide, derived from a measles phosphoprotein, ASDVETAEGGEIHELLRLQ (P1, residues 179-197), exhibited the capacity to stimulate peripheral blood mononuclear cells to proliferate. Our data provides direct evidence that the antigenic peptide of measles virus was processed by antigen-presenting cells, presented in the context of HLA class II molecules, and was recognized by peripheral blood T cells from healthy individuals previously immunized with measles vaccine. The approach described herein provides a useful methodology for the future identification of HLA-presented pathogen-derived epitopes using mass spectrometry. The study of cell-mediated immune responses to the measles-derived peptide in immune persons should provide significant insight into the design and development of new vaccines

  8. Prediction of spurious HLA class II typing results using probabilistic classification.

    Science.gov (United States)

    Schöfl, Gerhard; Schmidt, Alexander H; Lange, Vinzenz

    2016-03-01

    While modern high-throughput sequence-based HLA genotyping methods generally provide highly accurate typing results, artefacts may nonetheless arise for numerous reasons, such as sample contamination, sequencing errors, read misalignments, or PCR amplification biases. To help detecting spurious typing results, we tested the performance of two probabilistic classifiers (binary logistic regression and random forest models) based on population-specific genotype frequencies. We trained the model using high-resolution typing results for HLA-DRB1, DQB1, and DPB1 from large samples of German, Polish and UK-based donors. The high predictive capacity of the best models replicated both in 10-fold cross-validation for each gene and in using independent evaluation data (AUC 0.820-0.893). While genotype frequencies alone provide enough predictive power to render the model generally useful for highlighting potentially spurious typing results, the inclusion of workflow-specific predictors substantially increases prediction specificity. Low initial DNA concentrations in combination with low-volume PCR reactions form a major source of stochastic error specific to the Fluidigm chip-based workflow at DKMS Life Science Lab. The addition of DNA concentrations as a predictor variable thus substantially increased AUC (0.947-0.959) over purely frequency-based models. PMID:26826450

  9. Alloactivated HLA class II-positive T-cell lines induce IL-2 reactivity but lack accessory cell function in mixed leukocyte culture

    DEFF Research Database (Denmark)

    Odum, N; Dickmeiss, E; Hofmann, B;

    1989-01-01

    nonirradiated Ta stimulated primed lymphocytes directed against the relevant HLA class II antigens on the Ta. Interferon-gamma, recombinant interleukin 1, phorbol myristate acetate, calcium ionophore, and adherent cells had no effect on the stimulatory capability of Ta. The ability of irradiated Ta to stimulate...

  10. Transfusion Related Acute Lung Injury: A severe case triggered with anti-HLA class II antibodies in the recipient

    Directory of Open Access Journals (Sweden)

    Hale Borazan

    2012-04-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. The classic TRALI syndrome is characterized by the suddenly onset of respiratory failure within 2-6 hrs of the transfusion of a blood product, generally transient, resolves within 48-96 hrs spontaneously, and has a better prognosis. Nonetheless there is an expanded definition of TRALI syndrome up to 72 hrs, which is called delayed TRALI. The potential causes of TRALI can be explained by two distinct mechanism including the anti-leukocyte antibodies in donor plasma or in recipient plasma with the reverse mechanism, and biological response modifiers in susceptible individuals. This report highlights the succesful management of a classic TRALI case that was seen approximately two hours after the transfusion of a packed red blood cell and triggered with anti-HLA class II antibodies in the recipient with reverse mechanism accompanied by neutropenia together.

  11. AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIVcpz

    OpenAIRE

    de Groot, Natasja G.; Corrine M C Heijmans; Zoet, Yvonne M.; de Ru, Arnoud H.; Verreck, Frank A.; van Veelen, Peter A.; Drijfhout, Jan W; Doxiadis, Gaby G M; Remarque, Edmond J.; Doxiadis, Ilias I. N.; van Rood, Jon J.; Koning, Frits; Bontrop, Ronald E

    2010-01-01

    In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show tha...

  12. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D.

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2009-02-01

    Full Text Available Multiple sclerosis (MS is a complex trait in which allelic variation in the MHC class II region exerts the single strongest effect on genetic risk. Epidemiological data in MS provide strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of this disease. Growing evidence implicates sunlight or vitamin D as a key environmental factor in aetiology. We hypothesised that this environmental candidate might interact with inherited factors and sought responsive regulatory elements in the MHC class II region. Sequence analysis localised a single MHC vitamin D response element (VDRE to the promoter region of HLA-DRB1. Sequencing of this promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes. In contrast, there was striking variation among non-MS-associated haplotypes. Electrophoretic mobility shift assays showed specific recruitment of vitamin D receptor to the VDRE in the HLA-DRB1*15 promoter, confirmed by chromatin immunoprecipitation experiments using lymphoblastoid cells homozygous for HLA-DRB1*15. Transient transfection using a luciferase reporter assay showed a functional role for this VDRE. B cells transiently transfected with the HLA-DRB1*15 gene promoter showed increased expression on stimulation with 1,25-dihydroxyvitamin D3 (P = 0.002 that was lost both on deletion of the VDRE or with the homologous "VDRE" sequence found in non-MS-associated HLA-DRB1 haplotypes. Flow cytometric analysis showed a specific increase in the cell surface expression of HLA-DRB1 upon addition of vitamin D only in HLA-DRB1*15 bearing lymphoblastoid cells. This study further implicates vitamin D as a strong environmental candidate in MS by demonstrating direct functional interaction with the major locus determining genetic susceptibility. These findings support a connection between the main epidemiological and

  13. HLA-E: strong association with beta2-microglobulin and surface expression in the absence of HLA class I signal sequence-derived peptides

    Czech Academy of Sciences Publication Activity Database

    Lo Monaco, E.; Sibilio, L.; Melucci, E.; Tremante, E.; Suchánek, M.; Hořejší, Václav; Martayan, A.; Giacomini, P.

    2008-01-01

    Roč. 181, č. 8 (2008), s. 5442-5450. ISSN 0022-1767 Institutional research plan: CEZ:AV0Z50520514 Keywords : HLA-E * MHC * monoclonal antibodies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.000, year: 2008

  14. Altered HLA Class I Profile Associated with Type A/D Nucleophosmin Mutation Points to Possible Anti-Nucleophosmin Immune Response in Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Kateřina Kuželová

    Full Text Available Nucleophosmin 1 (NPM1 mutations are frequently found in patients with acute myeloid leukemia (AML and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+, a cohort of patients with wild-type NPM1 (94 patients, NPMwt and in normal individuals (large datasets available from Allele Frequency Net Database. Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B(*07, B(*18, and B(*40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein.

  15. Exploiting HLA-class II disparity for anti-tumor immunity by allogeneic cellular immunotherapy

    OpenAIRE

    Stevanović, Sanja

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment for various hematological malignancies. The beneficial Graft-versus-Leukemia (GvL) effect of alloSCT is mediated by donor-derived allo-reactive T cells targeting the malignant cells of the patient. Unfortunately, detrimental Graft-versus-Host-Disease (GvHD) often co-develops due to recognition of allo-antigens by donor-derived T cells on non-hematopoietic tissues. To prevent the development of GvH...

  16. HLA class II DR-DQ amino acids and insulin-dependent diabetes mellitus: Application of the haplotype method

    Energy Technology Data Exchange (ETDEWEB)

    Valdes, A.M.; McWeeney, S.; Thomson, G. [Univ. of California, Berkeley, CA (United States)

    1997-03-01

    Insulin-dependent diabetes mellitus (IDDM) HLA class III DRB1-DQA1-DQB1 data from four populations (Norwegian, Sardinian, Mexican American, and Taiwanese) have been analyzed to detect the amino acids involved in the disease process. The combination of sites DRB1 No. 67 and 86; DQA1 No. 47; and DQB1 No. 9, 26, 57, and 70 predicts the IDDM component in these four populations, when the results and criteria of the haplotype method for amino acids, developed in the companion paper in this issue of the journal, are used. The following sites, either individually, or in various combinations, previously have been suggested as IDDM components: DRB1 No. 57, 70, 71, and 86; DQA1 No. 52; and DQB1 No. 13, 45, and 57 (DQB1 No. 13 and 45 correlates 100% with DQB1 No. 9 and 26). We propose that DQA1 No. 47 is a better predictor of IDDM than is the previously suggested DQA1 No. 52, and we add DRB1 No. 67 and DQB1 No. 70 to the HLA DR-DQ IDDM amino acids. We do not claim to have identified all HLA DR-DQ amino acids - or highly correlated sites - involved in IDDM. The frequencies and predisposing/protective effects of the haplotypes defined by these seven sites have been compared, and the effects on IDDM are consistent across the populations. The strongest susceptible effects came from haplotypes DRB1*0301/DQA1*0501/ DQB1*0201 and DRB1*0401-5-7-8/DQA1*0301/DQB1*0302. The number of strong protective haplotypes observed was larger than the number of susceptible ones; some of the predisposing haplotypes were present in only one or two populations. Although the sites under consideration do not necessarily have a functional involvement in IDDM, they should be highly associated with such sites and should prove to be useful in risk assessment. 48 refs., 2 figs., 4 tabs.

  17. Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

    Directory of Open Access Journals (Sweden)

    Luciano Potena

    2013-01-01

    Full Text Available HLA antibodies (HLA ab in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed (52±13y; 16% females; 47% ischemic etiology, 32 (18% showed pretransplant HLA ab, and 12 (7% tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without (65±9 versus 82±3%; P=0.02, accounting for a doubled independent mortality risk (P=0.04. In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; P=0.05 and late cellular rejection (29 versus 11%; P=0.03. Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR, the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 (P=0.04. By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients.

  18. Type 1 Diabetes in the Spanish Population: additional factors to Class II HLA-DR3 and -DR4

    Directory of Open Access Journals (Sweden)

    Ibarra José M

    2005-04-01

    Full Text Available Abstract Background The Major Histocompatibility Complex is the main genetic contributor to susceptibility to type 1 diabetes (T1D; genome-wide scans have consistently mapped increased predisposition to this region. The highest disease risk has been associated with HLA-DR3 and HLA-DR4. In particular, the DR3-positive ancestral haplotype 18.2 was reported as highly diabetogenic. We aimed to corroborate whether this haplotype increases the susceptibility conferred by the DQ2-DR3 alleles in a Mediterranean population. We also searched for additional susceptibility factors to the classic DQ2-DR3 and DQ8-DR4. Results Genetic MHC markers were analysed in a case-control study with 302 T1D patients and 529 ethnically matched controls. DR3-TNFa1b5 carrier rate was significantly higher in DR3-positive heterozygous T1D patients than in DR3-positive heterozygous controls (p = 0.0019; odds ratio OR [95% confidence interval CI] = 2.26 [1.3–3.93]. This data was confirmed analysing the allelic frequency, which includes the information corresponding to the DR3-homozygous individuals (p = 0.001; OR = 2.09 and by using the Arlequin software to check the DR3-positive haplotypes (p = 0.004;OR = 1.93. The present results provide strong evidence of a second susceptibility region in the ancestral haplotype 18.2 in the Spanish population. Moreover, we searched for T1D susceptibility factors in addition to the MHC classical ones, within the DR2-DQ6/DR3-DQ2/DR4-DQ8 negative population. Several genetic markers in both MHC class II (DQA1*0101-DQB1*0501 [p = 0.007;OR = 2.81], DQA1*0201-DQB1*0202 [p = 0.03; OR = 2.35] and III (TNFa2b1 [p = 0.01 OR = 2.74], BAT-2*2 [p = 0.004; OR = 3.19] were found. These different alleles associated with T1D were not independent and we observed linkage disequilibrium among them leading us to describe two new risk haplotypes (DQA1*0101-DQB1*0501-TNFa2b1 and DQA1*0201-DQB1*0202- BAT-2*2. Finally, we studied a T1D susceptibility

  19. DNA polymorphism of HLA class II genes in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Cowland, J B; Andersen, V; Halberg, P;

    1994-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA-DRB, -DQA, -DQB, -DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3......- and DRw6-associated 7.00 kb DRB TaqI DNA fragment was found in SLE patients compared to normal controls (83.3% vs 35.5%; RR = 9.1, p < 10(-4). The frequencies of the DQA1*0501-associated 4.56 kb DQA TaqI fragment and the DRB3*01/03-associated 9.79 kb TaqI fragment were also found to be significantly...... increased in SLE patients (70.8% vs 29.7%; RR = 5.8, p < 10(-2) for the DQA fragment and 70.8% vs 36.1%; RR = 4.3, p < 0.05 for the DRB3 fragment). Less extensive and insignificant increases of the frequencies of the DR3-associated DQB and DPB fragments were observed. The frequencies of the DR2-associated...

  20. HLA class II genes polymorphism in DR4 giant cell arteritis patients.

    Science.gov (United States)

    Bignon, J D; Ferec, C; Barrier, J; Pennec, Y; Verlingue, C; Cheneau, M L; Lucas, V; Muller, J Y; Saleun, J P

    1988-11-01

    We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls. PMID:2906182

  1. HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

    Science.gov (United States)

    Ombrello, Michael J.; Remmers, Elaine F.; Tachmazidou, Ioanna; Grom, Alexei; Foell, Dirk; Haas, Johannes-Peter; Martini, Alberto; Gattorno, Marco; Özen, Seza; Prahalad, Sampath; Zeft, Andrew S.; Bohnsack, John F.; Mellins, Elizabeth D.; Ilowite, Norman T.; Russo, Ricardo; Len, Claudio; Hilario, Maria Odete E.; Oliveira, Sheila; Yeung, Rae S. M.; Rosenberg, Alan; Wedderburn, Lucy R.; Anton, Jordi; Schwarz, Tobias; Hinks, Anne; Bilginer, Yelda; Park, Jane; Cobb, Joanna; Satorius, Colleen L.; Han, Buhm; Baskin, Elizabeth; Signa, Sara; Duerr, Richard H.; Achkar, J. P.; Kamboh, M. Ilyas; Kaufman, Kenneth M.; Kottyan, Leah C.; Pinto, Dalila; Scherer, Stephen W.; Alarcón-Riquelme, Marta E.; Docampo, Elisa; Estivill, Xavier; Gül, Ahmet; de Bakker, Paul I. W.; Raychaudhuri, Soumya; Langefeld, Carl D.; Thompson, Susan; Zeggini, Eleftheria; Thomson, Wendy; Kastner, Daniel L.; Woo, Patricia

    2015-01-01

    Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10−17, odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10−5, OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10−16, OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11—HLA-DQA1*05—HLA-DQB1*03 haplotype [6.4 × 10−17, OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA. PMID:26598658

  2. The role of HLA class II genes in insulin-dependent diabetes mellitus: Molecular analysis of 180 Caucasian, multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Noble, J.A.; Cook, M.; Erlich, H.A. [Roche Molecular Systems, Alameda, CA (United States)]|[Children`s Hospital Oakland Research Institute, CA (United States)] [and others

    1996-11-01

    We report here our analysis of HLA class II alleles in 180 Caucasian nuclear families with at least two children with insulin-dependent diabetes mellitus (IDDM). DRB1, DQA1, DQB1, and DPB1 genotypes were determined with PCR/sequence-specific oligonucleotide probe typing methods. The data allowed unambiguous determination of four-locus haplotypes in all but three of the families. Consistent with other studies, our data indicate an increase in DR3/DR4, DR3/DR3, and DR4/DR4 genotypes in patients compared to controls. In addition, we found an increase in DR1/DR4, DR1/DR3, and DR4/DR8 genotypes. While the frequency of DQB1*0302 on DR4 haplotypes is dramatically increased in DR3/DR4 patients, DR4 haplotypes in DR1/DR4 patients exhibit frequencies of DQB1*0302 and DQB1*0301 more closely resembling those in control populations. The protective effect of DR2 is evident in this data set and is limited to the common DRB1*1501-DQB1*0602 haplotype. Most DR2{sup +} patients carry the less common DR2 haplotype DRB1*1601-DQB1*0502, which is not decreased in patients relative to controls. DPB1 also appears to play a role in disease susceptibility. DPB1*0301 is increased in patients (P < .001) and may contribute to the disease risk of a number of different DR-DQ haplotypes. DPB1*0101, found almost exclusively on DR3 haplotypes in patients, is slightly increased, and maternal transmissions of DRB1*0301-DPB1*0101 haplotypes to affected children occur twice as frequently as do paternal transmissions. Transmissions of DR3 haplotypes carrying other DPB1 alleles occur at approximately equal maternal and paternal frequencies. The complex, multigenic nature of HLA class II-associated IDDM susceptibility is evident from these data. 76 refs., 1 fig., 7 tabs.

  3. HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission.

    Directory of Open Access Journals (Sweden)

    Ma Luo

    Full Text Available HLA class II antigens are central in initiating antigen-specific CD4+ T cell responses to HIV-1. Specific alleles have been associated with differential responses to HIV-1 infection and disease among adults. This study aims to determine the influence of HLA class II genes and their interactive effect on mother-child perinatal transmission in a drug naïve, Mother-Child HIV transmission cohort established in Kenya, Africa in 1986. Our study showed that DRB concordance between mother and child increased risk of perinatal HIV transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83. Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no significant influence on perinatal HIV transmission. In addition, stratified analysis showed that DRB1*15:03+ phenotype (mother or child significantly increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1 discordance between mother and child provided 5 fold protection (P = 0.00008, OR: 0.186, 95%CI: 0.081-0.427. However, the protective effect of DRB discordance was diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49-0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956. DRB3+ children were less likely to be infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642. However, there is a 4 fold increase in risk of being infected at birth if DRB3+ children were born to DRB1*15:03+ mother compared to those with DRB1*15:03- mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children's DRB3 phenotype and their interactions play an important role in perinatal HIV transmission. Identification of genetic factors associated with protection or increased risk in perinatal transmission will help develop alternative prevention and treatment methods in the event of increases in drug resistance of ARV.

  4. Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

    2010-03-08

    Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

  5. Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition

    OpenAIRE

    1992-01-01

    The routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein (F) of measles virus (MV) to HLA class I and class II presentable peptides have been examined, using cloned cytotoxic T lymphocytes in functional assays. Presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines was achieved using live virus, ultraviolet light-inactivated virus, and purified MV- F delivered either as such or incorporated in immunostimulating complexes (MV-F-ISCO...

  6. Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis.

    Science.gov (United States)

    van Luijn, Marvin M; Kreft, Karim L; Jongsma, Marlieke L; Mes, Steven W; Wierenga-Wolf, Annet F; van Meurs, Marjan; Melief, Marie-José; der Kant, Rik van; Janssen, Lennert; Janssen, Hans; Tan, Rusung; Priatel, John J; Neefjes, Jacques; Laman, Jon D; Hintzen, Rogier Q

    2015-06-01

    C-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 its potential contribution to these diseases in humans are poorly understood. In this study, we found a strong upregulation of CLEC16A expression in the white matter of multiple sclerosis patients (n = 14) compared to non-demented controls (n = 11), mainly in perivascular leukocyte infiltrates. Moreover, CLEC16A levels were significantly enhanced in peripheral blood mononuclear cells of multiple sclerosis patients (n = 69) versus healthy controls (n = 46). In peripheral blood mononuclear cells, CLEC16A was most abundant in monocyte-derived dendritic cells, in which it strongly co-localized with human leukocyte antigen class II. Treatment of these professional antigen-presenting cells with vitamin D, a key protective environmental factor in multiple sclerosis, downmodulated CLEC16A in parallel with human leukocyte antigen class II. Knockdown of CLEC16A in distinct types of model and primary antigen-presenting cells resulted in severely impaired cytoplasmic distribution and formation of human leucocyte antigen class II-positive late endosomes, as determined by immunofluorescence and electron microscopy. Mechanistically, CLEC16A participated in the molecular machinery of human leukocyte antigen class II-positive late endosome formation and trafficking to perinuclear regions, involving the dynein motor complex. By performing co-immunoprecipitations, we found that CLEC16A directly binds to two critical members of this complex, RILP and the HOPS complex. CLEC16A silencing in antigen-presenting cells disturbed RILP-mediated recruitment of human leukocyte antigen class II-positive late endosomes to perinuclear regions. Together, we identify CLEC16A as a pivotal gene in multiple sclerosis

  7. Immunogenetics of rheumatoid arthritis and primary Sjögren's syndrome: DNA polymorphism of HLA class II genes

    DEFF Research Database (Denmark)

    Morling, Niels; Andersen, V; Fugger, L;

    1992-01-01

    . The frequencies of DNA fragments associated with the following HLA class II genes were increased in RA when compared to normal controls: DRB1*04 (DR4) (relative risk, RR = 7.4, P less than 10(-3), DRB4*0101 (DRw53) (RR = 9.6, P less than 10(-3), DQA1*0301 (RR = 9.6, P less than 10(-3), DQB1*0301 (DQw7) (RR = 2.......8, P less than 0.05, 'corrected' P greater than 0.05), and DQB1*0302 (DQw8) (RR = 4.5, P less than 10(-2). Negative associations were found between RA and DRB1*1501 (DR2/DRw15) (RR = 0.2, P less than 10(-2) and DQB1*0602 (DQw6) (RR = 0.2, P less than 10(-2), 'corrected' P greater than 0......(-3). Positive associations were found between primary SS and DNA fragments associated with DRB1*03/13 (RR = 6.8, P less than 10(-3), DRB3*0101 (DRw52) (RR = 5.7, P less than 10(-2), DQA1*0501 (RR = 6.8, P less than 10(-3), DQB1*0201 (DQw2) (RR = 11.6, P less than 10(-5), and DQB1*0602 (DQw6) (RR = 2.7, P less...

  8. Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma.

    Science.gov (United States)

    Shiraishi, Kouya; Okada, Yukinori; Takahashi, Atsushi; Kamatani, Yoichiro; Momozawa, Yukihide; Ashikawa, Kyota; Kunitoh, Hideo; Matsumoto, Shingo; Takano, Atsushi; Shimizu, Kimihiro; Goto, Akiteru; Tsuta, Koji; Watanabe, Shun-Ichi; Ohe, Yuichiro; Watanabe, Yukio; Goto, Yasushi; Nokihara, Hiroshi; Furuta, Koh; Yoshida, Akihiko; Goto, Koichi; Hishida, Tomoyuki; Tsuboi, Masahiro; Tsuchihara, Katsuya; Miyagi, Yohei; Nakayama, Haruhiko; Yokose, Tomoyuki; Tanaka, Kazumi; Nagashima, Toshiteru; Ohtaki, Yoichi; Maeda, Daichi; Imai, Kazuhiro; Minamiya, Yoshihiro; Sakamoto, Hiromi; Saito, Akira; Shimada, Yoko; Sunami, Kuniko; Saito, Motonobu; Inazawa, Johji; Nakamura, Yusuke; Yoshida, Teruhiko; Yokota, Jun; Matsuda, Fumihiko; Matsuo, Keitaro; Daigo, Yataro; Kubo, Michiaki; Kohno, Takashi

    2016-01-01

    Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10(-17), per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10(-9), per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations. PMID:27501781

  9. Differences in the expressed HLA class I alleles effect the differential clustering of HIV type 1-specific T cell responses in infected Chinese and Caucasians

    Institute of Scientific and Technical Information of China (English)

    Yu,XG; Addo,MM; Perkins,BA; Wej,FL; Rathod,A; Geer,SC; Parta,M; Cohen,D; Stone,DR; Russell,CJ; Tanzi,G; Mei,S; Wureel,AG; Frahm,N; Lichterfeld,M; Heath,L; Mullins,JI; Marincola,F; Goulder,PJR; Brander,C; Allen,T; Cao,YZ; Walker,BD; Altfeld,M

    2005-01-01

    China is a region of the world with a rapidly spreading HIV-1 epidemic. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to support the design and testing of an effective HIV-1 vaccine for this population. HIV-1-specific T cell responses were characterized in 32 HIV-1-infected individuals of Chinese origin and compared to 34 infected caucasians using 410 overlapping peptides spanning the entire HIV-1 clade B consensus sequence in an IFN-gamma ELISpot assay. All HIV-1 proteins were targeted with similar frequency in both populations and all study subjects recognized at least one overlapping peptide. HIV-1-specific T cell responses clustered in seven different regions of the HIV-1 genome in the Chinese cohort and in nine different regions in the caucasian cohort. The dominant HLA class I alleles expressed in the two populations differed significantly, and differences in epitope clustering pattern were shown to be influenced by differences in class I alleles that restrict immunodominant epitopes. These studies demonstrate that the clustering of HIV-1-specific T cell responses is influenced by the genetic HLA class I background in the study populations. The design and testing of candidate vaccines to fight the rapidly growing HIV-1 epidemic must therefore take the HLA genetics of the population into account as specific regions of the virus can be expected to be differentially targeted in ethnically diverse populations.

  10. Detection of newly antibody-defined epitopes on HLA class I alleles reacting with antibodies induced during pregnancy.

    Science.gov (United States)

    Duquesnoy, R J; Hönger, G; Hösli, I; Marrari, M; Schaub, S

    2016-08-01

    The determination of HLA mismatch acceptability at the epitope level can be best performed with epitopes that have been verified experimentally with informative antibodies. The website-based International Registry of HLA Epitopes (http://www.epregistry.com.br) has a list of 81 antibody-verified HLA-ABC epitopes but more epitopes need to be added. Pregnancy offers an attractive model to study antibody responses to mismatched HLA epitopes which can be readily determined from the HLA types of child and mother. This report describes a HLAMatchmaker-based analysis of 16 postpregnancy sera tested in single HLA-ABC allele binding assays. Most sera reacted with alleles carrying epitopes that have been antibody-verified, and this study focused on the reactivity of additional alleles that share other epitopes corresponding to eplets and other amino acid residue configurations. This analysis led in the identification of 16 newly antibody-defined epitopes, seven are equivalent to eplets and nine correspond to combinations of eplets in combination with other nearby residue configurations. These epitopes will be added to the repertoire of antibody-verified epitopes in the HLA Epitope Registry. PMID:27312793

  11. A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.

    Directory of Open Access Journals (Sweden)

    Susan Pereira Ribeiro

    Full Text Available Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8. Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.

  12. Human epidermal Langerhans cells cointernalize by receptor-mediated endocytosis "nonclassical" major histocompatibility complex class I molecules (T6 antigens) and class II molecules (HLA-DR antigens).

    OpenAIRE

    Hanau, D.; Fabre, M.; Schmitt, D A; Garaud, J C; Pauly, G; Tongio, M M; Mayer, S.; Cazenave, J. P.

    1987-01-01

    HLA-DR and T6 surface antigens are expressed only by Langerhans cells and indeterminate cells in normal human epidermis. We have previously demonstrated that T6 antigens are internalized in Langerhans cells and indeterminate cells by receptor-mediated endocytosis. This process is induced by the binding of BL6, a monoclonal antibody directed against T6 antigens. In the present study, using a monoclonal antibody directed against HLA-DR antigens, on human epidermal cells in suspension, we show t...

  13. Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22 (q34;q11

    Directory of Open Access Journals (Sweden)

    Cano Pedro

    2004-06-01

    Full Text Available Abstract Background Based on the site of breakpoint in t(9;22 (q34;q11, bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. Methods The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Results Significant negative associations (p Conclusions The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22 (q34;q11-positive leukemia.

  14. Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

    International Nuclear Information System (INIS)

    Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

  15. The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.

    Science.gov (United States)

    Solomon, Christopher; Southwood, Scott; Hoof, Ilka; Rudersdorf, Richard; Peters, Bjoern; Sidney, John; Pinilla, Clemencia; Marcondes, Maria Cecilia Garibaldi; Ling, Binhua; Marx, Preston; Sette, Alessandro; Mothé, Bianca R

    2010-07-01

    Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus macaque potentially being a more relevant model for AIDS outcomes than the Indian rhesus macaque, the Chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility complex (MHC) composition and function, reducing their greater utilization. In this study, we characterized a total of 50 unique Chinese rhesus macaques from several varying origins for their entire MHC class I allele composition and identified a total of 58 unique complete MHC class I sequences. Only nine of the sequences had been associated with Indian rhesus macaques, and 28/58 (48.3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide binding characteristics with the HLA-B7 supertype, the most frequent supertype in human populations. These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques. PMID:20480161

  16. HLA class II immunogenetics and incidence of insulin-dependent diabetes mellitus in the population of Cantabria (Northern Spain).

    Science.gov (United States)

    Escribano-de-Diego, J; Sánchez-Velasco, P; Luzuriaga, C; Ocejo-Vinyals, J G; Paz-Miguel, J E; Leyva-Cobián, F

    1999-10-01

    HLA class II genes were analyzed to study IDDM susceptibility in Cantabria (Northern Spain). Patients showed highly significant increases in DRB1*0301 (RR = 4.581, p < 0.00005), DRB1*0401 (RR = 2.6, p < 0.05), DRB1*0402 (RR = 8.78, p < 0.05) and DRB1*0405 (RR = 14.73, p < 0.005). Highly significant diferences were in the DQA1*0301 (RR = 3.62, p < 0.000005) and DQA1*0501 (RR = 2.13, p < 0.05) alleles. DQB*0201 (RR = 4.1, p < 0.00005) and DQB1*0302 (RR = 5.42, p < 0.000005) alleles were also significantly increased. A significant increase in DRB1*0402-DQA1*0301-DQB1*0302 (RR = 16.18, p < 0.05), DRB1*0405-DQA1*0301-DQB1*0302 (RR = 16.12, p < 0.05), DRB1*0301-DQA1*0501-DQB1*0201 (RR = 4.58, p < 0.00005) and DRB1*0401-DQA1*0301-DQB1*0302 (RR = 4.36, p < 0.005) was apparent in the diabetic group, while the DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1401-DQA *0104-DQB1*05031 protective haplotypes (RR = 0.17 and 0.09, p < 0.0005 and 0.05, respectively) were significantly lower in patients. The absence of Asp57 and the presence of Arg52 were associated with disease in a dose-dependent manner. Several genotypes encoding the identical DQalpha52/DQbeta57 phenotype carried very different RRs. Finally, the Cantabrian population has the highest incidence of IDDM reported for Spain (15.2 of 100.000 in the 0-14 age group, Poisson's 95% CI: 10.6-19.3). PMID:10566601

  17. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

    Directory of Open Access Journals (Sweden)

    Chandra M Ohri

    Full Text Available BACKGROUND: We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM expression of proteins associated with M1 and M2 macrophages in NSCLC. METHODS: Using immunohistochemistry, CD68(+ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14, or a non-cytotoxic M2 phenotype (CD163 and VEGF were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES (median 92.7 months and 20 patients with poor survival (PS (median 7.7 months. RESULTS: The NM expression of NM-HLA-DR (p<0.001, NM-iNOS (p = 0.02 and NM-MRP 8/14 (p = 0.02 was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001. There was more NM-CD163 expression (p = 0.04 but less NM-iNOS (p = 0.002 and MRP 8/14 (p = 0.01 expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001, 65.0% versus 14.6% (NM-iNOS p = 0.003, and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04, as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41 and 19.4% versus 59.0% (NM-VEGF p = 0.001. CONCLUSIONS: Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

  18. Aloimunidade contra antígenos HLA de classe I em pacientes com síndromes mielodisplásicas e anemia aplástica Aloimmunity against HLA class I antigens in patients with myelodisplastic syndrome and aplastic anemia

    Directory of Open Access Journals (Sweden)

    Daisy M. M. Arruda

    2008-02-01

    Full Text Available As síndromes mielodisplásicas (SMD e a anemia aplástica (AA apresentam citopenias periféricas necessitando, com freqüência, de reposições transfusionais contínuas de concentrados de hemácias e/ou de concentrados de plaquetas. O objetivo do presente estudo foi verificar a ocorrência de anticorpos anti-HLA de classe I em pacientes portadores das SMD e AA atendidos no ambulatório de Hematologia do Hemoce/UFC. Foram analisados 110 pacientes, sendo 70 com SMD e 40 com AA. A pesquisa de anticorpos anti-HLA de classe I foi realizada frente a um painel (PRA, utilizando-se a técnica de microlinfocitotoxicidade dependente do complemento. Vinte (28,6% dos 70 pacientes com as SMD e 18 (45% dos 40 pacientes com AA desenvolveram anticorpos anti-HLA contra o PRA. Esses pacientes que receberam uma carga de antígenos estranhos advindos de múltiplas transfusões de vários doadores de CH e/ou CP, geralmente desenvolvem aloanticorpos contra os antígenos HLA presentes na superfície das plaquetas e dos leucócitos que contaminam esses concentrados. A produção desses anticorpos pode trazer sérias complicações para o tratamento dos pacientes com SMD e AA. As avaliações sistemáticas para detecção de anticorpos anti-HLA após a reposição transfusional podem ser valiosas para adoção de estratégias transfusionais mais adequadas para esta população de pacientes.Patients with myelodysplastic syndromes (MDS or aplastic anemia (AA present peripheral cytopenias and require continuous transfusions of red cell and/or platelet concentrates. The objective of this study is to verify the existence of anti-HLA class 1 antibodies in patients with MDS and AA treated at the hematology Out patient Clinic of Hemoce/UFC. A total of 110 patients were analyzed, 70 with MDS and 40 with AA. Anti-HLA class 1 antibody detection was achieved with an antibody reactivity panel using the complement-dependent microlymphocytotoxicity technique. A total of 20 (28.6% of

  19. NetMHCpan, a method for MHC class I binding prediction beyond humans

    DEFF Research Database (Denmark)

    Hoof, Ilka; Peters, B; Sidney, J;

    2009-01-01

    Binding of peptides to major histocompatibility complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC genomic region (called HLA) is extremely polymorphic comprising several thousand alleles, each encoding a distinct...... method that generates quantitative predictions of the affinity of any peptide-MHC class I interaction. NetMHCpan-2.0 has been trained on the hitherto largest set of quantitative MHC binding data available, covering HLA-A and HLA-B, as well as chimpanzee, rhesus macaque, gorilla, and mouse MHC class I...... molecules. We show that the NetMHCpan-2.0 method can accurately predict binding to uncharacterized HLA molecules, including HLA-C and HLA-G. Moreover, NetMHCpan-2.0 is demonstrated to accurately predict peptide binding to chimpanzee and macaque MHC class I molecules. The power of NetMHCpan-2.0 to guide...

  20. No difference in the parental origin of susceptibility HLA class II haplotypes among Norwegian patients with insulin-dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Undlien, D.E.; Akselsen, H.E.; Thorsby, E. [National Hospital, Oslo (Norway)] [and others

    1995-12-01

    Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease affecting genetically susceptible individuals. A major part of the genetic risk is encoded by HLA class II genes. Strong susceptibility is conferred by the DRB1*04-DQA1*03-DQB1*0302 (hereafter called {open_quotes}DR4-DQ8{close_quotes}) and the DRBI*0301-DQA1*0501-DQB1*0201 (hereafter called {open_quotes}DR3-DQ2{close_quotes}) haplotypes, particularly when they occur together. In an interesting publication it suggests that IDDM patients inherit DR4 from their fathers and DR3 from their mothers more often than vice versa. This has also been suggested elsewhere. Several different mechanisms have been proposed to explain this observation, such as parental imprinting, fetal loss, and maternal effect associated with the presence of the DR3 antigen in the mother. Several studies have shown that children of fathers with IDDM have a higher risk of IDDM than do children of mothers with IDDM. If there is an effect of the parental origin of HLA class II-encoded IDDM susceptibility, this could potentially explain the difference. 19 refs., 2 tabs.

  1. Estudio de la compatibilidad por métodos serológicos (HLA y celulares (CML en 22 años de trabajo en el Instituto de Hematología e Inmunología Study of compatibility by serological(HLAand cellular methods (MLC in 22 years of work in the Hematology and Immunology Institute

    Directory of Open Access Journals (Sweden)

    Luz M Morera Barrios

    2002-12-01

    Full Text Available Se estudió la histocompatibilidad de los loci ABC y del locus D del sistema principal de histocompatibilidad mediante las técnicas serológicas de microlinfocitotoxicidad en 383 pacientes con diferentes enfermedades hematológicas. Se comparó por la técnica celular y la reactividad linfocitaria en el cultivo mixto de linfocitos (CML de 39 de los 145 individuos idénticos para los antígenos HLA, de los estudios familiares realizados en el IHI, de los que resultaron 29 CML negativos, para el 74,35 %. No se correspondieron en el 100 % los estudios serológicos y celulares, ya que no se compatibilizó en todos los casos para los antígenos HLA de clase II, y en ninguno para los antígenos menores de histocompatibilidad, que influyen tanto en los resultados del CML, como en las causas de fracaso del trasplante de médula ósea (TMO en individuos idénticos. Esto corrobora la importancia de los estudios de tipificación de Biología Molecular y antígenos menores de histocompatibilidadThe histocompatibility of loci ABC and locus D of the main histocompatibility system was studied by serological techniques of microlymphocytotoxicity in 383 patients with various hematological diseases. Lymphocyte reactivity was compared in the mixed lymphocyte culture of 39 of 145 identical individuals for HLA antigens, of whom 29 were negative MLC for 74,35%. There was not 100% correspondence between serological and cellular studies since there was no compatibility in all the cases for HLA class II antigens and in any case for minor histocompatibility antigens that influence both the results of MLC and the causes of failed bone marrow transplantation in identical individuals. This confirms the importance of Molecular Biology typing studies and of minor histocompatibility antigens

  2. On the Global Dissipativity of a Class of Cellular Neural Networks with Multipantograph Delays

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    Liqun Zhou

    2011-01-01

    Full Text Available For the first time the global dissipativity of a class of cellular neural networks with multipantograph delays is studied. On the one hand, some delay-dependent sufficient conditions are obtained by directly constructing suitable Lyapunov functionals; on the other hand, firstly the transformation transforms the cellular neural networks with multipantograph delays into the cellular neural networks with constant delays and variable coefficients, and then constructing Lyapunov functionals, some delay-independent sufficient conditions are given. These new sufficient conditions can ensure global dissipativity together with their sets of attraction and can be applied to design global dissipative cellular neural networks with multipantograph delays and easily checked in practice by simple algebraic methods. An example is given to illustrate the correctness of the results.

  3. Pseudomonas aeruginosa Quorum Sensing Molecule N-(3-Oxododecanoyl)-L-Homoserine-Lactone Induces HLA-G Expression in Human Immune Cells.

    Science.gov (United States)

    Bortolotti, Daria; LeMaoult, Joel; Trapella, Claudio; Di Luca, Dario; Carosella, Edgardo D; Rizzo, Roberta

    2015-10-01

    HLA-G is a nonclassical class I human leukocyte antigen (HLA) involved in mechanisms of immune tolerance. The objective of this study was to determine whether N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL), a quorum sensing molecule produced by Pseudomonas aeruginosa, could modify HLA-G expression to control the host immune response. We evaluated the ability of 3O-C12-HSL to induce HLA-G expression in primary immune cells, monocytes (U937 and THP1), and T-cell lines (Jurkat) in vitro and analyzed the cellular pathway responsible for HLA-G expression. We studied the HLA-G promoter with a luciferase assay and interleukin-10 (IL-10) and p38/CREB signaling with enzyme-linked immunosorbent assay and immunofluorescence, respectively. We observed that 3O-C12-HSL is able to induce HLA-G expression in human monocytes and T cells. We showed that the induction of HLA-G by 3O-C12-HSL is p38/CREB and IL-10 dependent. 3O-C12-HSL treatment is able to arrest only the U937 cell cycle, possibly due to the peculiar expression of the ILT2 receptor in the U937 cell line. Our observations suggest HLA-G as a mechanism to create a protected niche for the bacterial reservoir, similar to the role of HLA-G molecules during viral infections. PMID:26195547

  4. Results of Expedicion Humana. I. Analysis of HLA class II (DRB1-DQA1-DPB1) alleles and DR-DQ haplotypes in nine Amerindian populations from Colombia.

    Science.gov (United States)

    Trachtenberg, E A; Keyeux, G; Bernal, J E; Rhodas, M C; Erlich, H A

    1996-09-01

    HLA class II variation was analyzed in nine Native American populations of Colombia using PCR/SSOP typing methods. Under the auspices of the Expedition Humana, approximately 30 unrelated native Colombia Indian samples each from the Tule (NW Pacific Coast), Kogui (Sierra Nevada). Ijka (Sierra Nevada), Ingano (Amazonas), Coreguaje (Amazonas), Nukak (Amazonas), Waunana (Pacific), Embera (Pacific) and Sikuani (Northeastern Plains) were collected and analyzed at the DRBI, DQA1, DQB1 and DPB1 loci. The number of different DRB1, DQA1, DQB1 and DPB1 alleles in the Colombian Indians is markedly reduced in comparison with neighboring African Colombian populations, which exhibit a very high degree of class II variability, as discussed in an accompanying paper. In the Colombian Amerindian groups, DR2 (DRB1*1602), DR4 (DRB1*0407, *0404, *0403 AND *0411), DR6 (DRB1*1402) and DR8 (DRB1*0802) comprise > 95% of all DRB1 alleles. We also found an absence of DR3 in all populations, and DR1, DR7 and DR9 allelic groups were either very rare or absent. Each Colombian Amerindian population has a predominant DRB1 allele (f = approximately 0.22-0.65) and DRB1-DQA1-DQB1 haplotype. Several novel DR-DQ haplotypes were also found. At the DPB1 locus, DPB1*0402 (f = 0.28-0.82), *1401 (f = 0.03-0.45), and *3501 (f = 0.03-0.27), were the three most prevalent alleles, each population maintaining one of these three alleles as the predominant (f > 0.26) DPB1 allele. The reduction of diversity for the HLA class II alleles in the Colombian Indians is suggestive of a population bottleneck during the colonization of the Americans, with little to no subsequent admixture with neighboring African Colombian populations in the last approximately 300 years. PMID:8896175

  5. Localization of the gene encoding the putative human HLA class II associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Fink, T.M.; Lichter, P. [Deutsches Krebsforschungszentrum Abt. Organisation komplexer Genome, Heidelberg (Germany); Vaesen, M. [Max-Planck-Institut fuer experimentelle Medizin Abt. Immunchemie, Goettingen (Germany)] [and others

    1995-09-01

    The putative HLA class II associated proteins PHAPI and PHAPII were purified and cloned on the basis of their ability to bind to the cytoplasmatic domain of the HLA Dr{alpha}-chain. They might be components of the transmembrane signaling pathway that is activated after extracellular binding of ligands during the immune response. Both proteins share extended stretches of highly acidic amino acids in their C-terminal regions that also indicate a nuclear localization. Indeed, PHAPI is likely to be the human homologue of the rat {open_quotes}leucine-rich acidic nuclear protein{close_quotes} (LANP) (83.6% amino acid identity), which was shown to be localized in the nuclei of Purkinje cells. Comparison of the cDNA sequences with entries in the EMBL data library revealed that PHAPII is identical to a protein named SET. The SET gene is located on chromosome 9q34 and was found to be fused to the putative oncogene CAN in one patient with acute undifferentiated leukemia (AUL). 9 refs., 1 fig.

  6. A New Humanized HLA Transgenic Mouse Model of Multiple Sclerosis Expressing Class II on Mouse CD4 T Cells

    OpenAIRE

    Mangalam, Ashutosh; Rodriguez, Moses; David, Chella

    2007-01-01

    Among all the genetic factors associated with MS susceptibility, strongest association has been seen with expression of certain MHC class II molecules, although analysis of their exact function remains complicated. In general expression of class II is restricted to professional antigen presenting cells, however human but not mice CD4+ T cells express class II on their surface. Functional studies of classII+CD4+ T cells have been hampered due to lack of proper animal model. Here we describe de...

  7. Human cytomegalovirus pp65- and immediate early 1 antigen-specific HLA class I-restricted cytotoxic T cell responses induced by cross-presentation of viral antigens.

    Science.gov (United States)

    Tabi, Z; Moutaftsi, M; Borysiewicz, L K

    2001-05-01

    Dendritic cells (DCs) play a pivotal role in the development of anti-viral CD8(+) CTL responses. This is straightforward if they are directly infected with virus, but is less clear in response to viruses that cannot productively infect DCS: Human CMV (HCMV) shows strain-specific cell tropism: fibroblast (Fb)-adapted laboratory strains (AD169) and recent clinical isolates do not infect DCs, whereas endothelial cell-adapted strains (TB40/E) result in productive lytic DC infection. However, we show here that uninfected DCs induce CD8(+) T cell cytotoxicity and IFN-gamma production against HCMV pp65 and immediate early 1 Ags following in vitro coculture with HCMV-AD169-infected Fbs, regardless of the HLA type of these FBS: CD8(+) T cell stimulation was inhibited by pretreatment of DCs with cytochalasin B or brefeldin A, indicating a phagosome/endosome to cytosol pathway. HCMV-infected Fbs were not apoptotic as measured by annexin V binding, and induction of apoptosis of infected Fbs in vitro did not augment CTL induction by DCs, suggesting a mechanism other than apoptosis in the initiation of cross-presentation. Furthermore, HCMV-infected Fbs provided a maturation signal for immature DCs during coculture, as evidenced by increased CD83 and HLA class II expression. Cross-presentation of HCMV Ags by host DCs enables these professional APCs to bypass some of the evasion mechanisms HCMV has developed to avoid T cell recognition. It may also serve to explain the presence of immediate early 1 Ag-specific CTLs in the face of pp65-induced inhibition of Ag presentation at the level of the infected cell. PMID:11313411

  8. Idiopathic focal segmental glomerulosclerosis and HLA antigens

    Directory of Open Access Journals (Sweden)

    M. Gerbase-DeLima

    1998-03-01

    Full Text Available The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS. HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P<0.05. In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease

  9. Human thymic epithelial cells express functional HLA-DP molecules

    DEFF Research Database (Denmark)

    Jørgensen, A; Röpke, C; Nielsen, M;

    1996-01-01

    HLA-DP molecules function as restriction elements in the presentation of foreign antigens to T cells by antigen presenting cells and certain HLA-DP molecules confer susceptibility to autoimmune disease. Because HLA molecules play an essential role in thymic selection and elimination of autoreactive...... T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DQ but lower than that of HLA-DR. Upon IFN-gamma treatment, HLA-DP expression was strongly upregulated. Since HLA-DQ and DR expression was upregulated in parallel, the hierarchy between MHC class II isotypes remained unchanged following interferon treatment. TEC elicited significant...

  10. Multiple HLA Epitopes Contribute to Type 1 Diabetes Susceptibility

    OpenAIRE

    Roark, Christina L.; Anderson, Kirsten M.; Simon, Lucas J.; Schuyler, Ronald P.; Aubrey, Michael T; Freed, Brian M.

    2013-01-01

    Disease susceptibility for type 1 diabetes is strongly associated with the inheritance of specific HLA alleles. However, conventional allele frequency analysis can miss HLA associations because many alleles are rare. In addition, disparate alleles that have similar peptide-binding sites, or shared epitopes, can be missed. To identify the HLA shared epitopes associated with diabetes, we analyzed high-resolution genotyping for class I and class II loci. The HLA epitopes most strongly associated...

  11. The peptide-binding specificity of HLA-A*3001 demonstrates membership of the HLA-A3 supertype

    DEFF Research Database (Denmark)

    Lamberth, K; Røder, G; Harndahl, M;

    2008-01-01

    Human leukocyte antigen class I (HLA-I) molecules are highly polymorphic peptide receptors, which select and present endogenously derived peptide epitopes to CD8+ cytotoxic T cells (CTL). The specificity of the HLA-I system is an important component of the overall specificity of the CTL immune...... system. Unfortunately, the large and rapidly increasing number of known HLA-I molecules seriously complicates a comprehensive analysis of the specificities of the entire HLA-I system (as of June 2008, the international HLA registry holds >1,650 unique HLA-I protein entries). In an attempt to reduce this...... complexity, it has been suggested to cluster the different HLA-I molecules into "supertypes" of largely overlapping peptide-binding specificities. Obviously, the HLA supertype concept is only valuable if membership can be assigned with reasonable accuracy. The supertype assignment of HLA-A*3001, a common HLA...

  12. Uncovering the Peptide-Binding Specificities of HLA-C: A General Strategy To Determine the Specificity of Any MHC Class I Molecule

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette;

    2014-01-01

    molecules. Assessing the functional significance of these new tools, HLA-C*07:01 transgenic mice were immunized with stable HLA-C*07:01 binders; six of six tested stable peptide binders were immunogenic. Finally, we generated HLA-C tetramers and labeled human CD8(+) T cells and NK cells. These new resources...... should support future research on the biology of HLA-C molecules. The data are deposited at the Immune Epitope Database, and the updated NetMHCpan predictor is available at the Center for Biological Sequence Analysis and the Immune Epitope Database....

  13. Up-regulation of HLA class-I antigen expression and antigen-specific CTL response in cervical cancer cells by the demethylating agent hydralazine and the histone deacetylase inhibitor valproic acid

    Directory of Open Access Journals (Sweden)

    Lizano-Soberón Marcela

    2006-12-01

    Full Text Available Abstract Background DNA hypermethylation and histone deacetylation are epigenetic events that contribute to the absence or downregulated expression of different components of the tumor recognition complex. These events affect the processing and presentation of antigenic peptides to CTLs by HLA class-I molecules. In this work evaluated the effect of the DNA hypomethylating agent hydralazine and the histone deacetylase inhibitor valproic acid, on the expression of HLA class-I molecules and on the antigen-specific immune recognition of cervical cancer cells. Methods Cell lines C33A (HPV-, CaSki (HPV-16+ and MS751 (HPV-18+ were treated with hydralazine and valproic acid to assess the expression of HLA class-I molecules by flow cytometry and RT-PCR. Promoter methylation of HLA class-I -A, -B and C, was also evaluated by Methylation-Specific PCR. Primary cervical tumors of four HLA-A*0201 allele patients were typed for HPV and their CTL's stimulated in vitro with the T2 cell line previously loaded with 50 μM of the HPV peptides. Cytotoxicity of stimulated CTL's was assayed against Caski and MS751 cells pre-treated with hydralazine and valproic acid. Results Valproic acid and hydralazine/valproic acid up-regulated the constitutive HLA class-I expression as evaluated by flow cytometry and RT-PCR despite constitutive promoter demethylation at these loci. Hydralazine and valproic acid in combination but no IFN-gamma hyperacetylated histone H4 as evaluated by ChiP assay. The antigenic immune recognition of CaSki and MS751 cells by CTLs specific to HPV-16/18 E6 and E7-derived epitopes, was increased by VA and H/VA and the combination of H/VA/IFN-gamma. Conclusion These results support the potential use of hydralazine and valproic acid as an adjuvant for immune intervention in cervical cancer patients whenever clinical protocols based on tumor antigen recognition is desirable, like in those cases where the application of E6 and E7 based therapeutic vaccines

  14. The two neutrophil plasma membrane markers alkaline phosphatase and HLA class I antigen localize differently in granule-deficient cytoplasts. An ideal plasma membrane marker in human neutrophils is still lacking.

    Science.gov (United States)

    Pellmé, Sara; Dahlgren, Claes; Karlsson, Anna

    2007-08-31

    Neutrophil function relies largely on the ability of the cell to mobilize its different granules and vesicles to the cell surface and thereby expose and/or release effector molecules to the surrounding tissue. To properly identify these subcellular compartments is thus a prerequisite for studies of neutrophil physiology. A range of specific markers for the classical granules is available, but finding optimal markers for the secretory vesicles and plasma membrane has historically been more challenging. Latent and non-latent alkaline phosphatase activities are often used to distinguish these two light membrane structures, but the outcome using this technique depends on the level of cellular activation. Therefore, HLA-I was introduced some years ago as a specific, stimulation-independent marker for the plasma membrane. In this study we however report that detailed fractionation studies of neutrophil cytoplasts, lacking secretory vesicles, granules and other dense organelles, reveal that the HLA-I antigen is not only co-localizing with the plasma membrane marker ALP, but is also present in other, more dense organelles. Further, we found the mixed enzyme-linked immunosorbent assay (MELISA), detecting the beta(2)-microglobulin/HLA-I complex, to be negatively influenced by uncomplexed beta(2)-microglobulin present in the specific granules and secretory vesicles, making it difficult to use HLA-I as a plasma membrane marker during maturation of for example phagolysosomes. PMID:17673253

  15. Extended HLA-D region haplotype associated with celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  16. HLA-G polymorphisms and HLA-G expression in sarcoidosis

    DEFF Research Database (Denmark)

    Hviid, TVF; Milman, N; Hylenius, S;

    2006-01-01

    BACKGROUND: The MHC class Ib molecule Human Leukocyte Antigen (HLA)-G may be important in induction and maintenance of immunological tolerance, and HLA-G expression may have a role in different cancers, in certain diseases with associations to HLA, and in organ transplantation. Sarcoidosis is a...... systemic granulomatous disease with unknown etiology but at the molecular level several studies have shown HLA associations. METHODS: In the present study, HLA-G alleles/polymorphisms were studied in sarcoidosis patients (n = 47) and controls (n = 129) by PCR techniques and HLA-G protein expression was...... investigated in granulomas from sarcoidosis patients with the use of immunohistochemistry. RESULTS: The HLA-G*010102/-G*0106 alleles were observed more often in sarcoidosis patients (39.4%) than in controls (26.4%), p = 0.025 (Fisher's exact test); however, not significant after correction (p(c) = 0.15). When...

  17. HLA and non-HLA genes in Behçet’s disease: a multicentric study in the Spanish population

    OpenAIRE

    Montes-Cano, Marco A.; Conde-Jaldón, Marta; García-Lozano, José R.; Ortiz-Fernández, Lourdes; Ortego-Centeno, Norberto; Castillo-Palma, María J.; Espinosa, Gerard; Graña-Gil, Genaro; Miguel A. González-Gay; Barnosi-Marín, Ana C.; Solans, Roser; Fanlo, Patricia; Camps, Teresa; Castañeda, Santos; Sánchez-Bursón, Juan

    2013-01-01

    Abstract Introduction According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet’s disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD...

  18. HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703

    DEFF Research Database (Denmark)

    Matthews, Philippa C; Adland, Emily; Listgarten, Jennifer;

    2011-01-01

    The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C......-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1...... disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag...

  19. HLA-DP, HLA-DQ, and HLA-DR-restricted epitopes in GRA5 of toxoplasma gondii strains

    Science.gov (United States)

    Haryati, S.; Sari, Y.; APrasetyo, A.; Sariyatun, R.

    2016-02-01

    The dense granular (GRA) proteins of Toxoplasma gondii(T. gondii) have been demonstrated as potential sources of T. gondii vaccine antigens. However, data of the GRA5 protein are limited. This study analyzed twenty-one complete GRA5 sequences of T. gondii GT1, RH, ME49, VEG, MAS, RUB, FOU, p89, VAND, and GAB2-2007-GAL-DOM2 strains to identify potential epitopes restricted by Major Histocompatibility Complex class II (MHC- II) molecules (human leukocyte antigen (HLA)-DP, HLA-DQ, and HLA-DR) in the protein. In all T. gondii strains, peptides positioned at amino acid (aa) 15-29, 16-30, 17-31, 18-32, 19-33, 83-97, 84-98, 86-100, 87-101, 89-103, and 90-104 were predicted to pose high affinity and binding with HLA-DRB1*0101, HLA-DRB1*0301 (DR17), HLA-DRB1*0401 (DR4Dw4), HLA-DRB1*0701, HLA-DRB1*1101, HLA-DRB1*1501 (DR2b), and/or HLA-DRB5*0101. Considering the epitope's affinity, ligation strength, and hydrophilicity, LRLLRRRRRRAIQEE sequence (aa 90-104) restricted by HLA-DRB1*0101, HlA- DRB1*0301 (DR17), and HLA-DRB1*0401 (DR4Dw4) was considered as the most potential MHC-II epitope in GRA5 of T. gondii. These results would be useful for studies concerning in developing T. gondii vaccine and diagnostic method.

  20. Complementarity of Binding Motifs is a General Property of HLA-A and HLA-B Molecules and Does Not Seem to Effect HLA Haplotype Composition.

    Science.gov (United States)

    Rao, Xiangyu; De Boer, Rob J; van Baarle, Debbie; Maiers, Martin; Kesmir, Can

    2013-01-01

    Different human leukocyte antigen (HLA) haplotypes (i.e., the specific combinations of HLA-A, -B, -DR alleles inherited together from one parent) are observed in different frequencies in human populations. Some haplotypes, like HLA-A1-B8, are very frequent, reaching up to 10% in the Caucasian population, while others are very rare. Numerous studies have identified associations between HLA haplotypes and diseases, and differences in haplotype frequencies can in part be explained by these associations: the stronger the association with a severe (autoimmune) disease, the lower the expected HLA haplotype frequency. The peptide repertoires of the HLA molecules composing a haplotype can also influence the frequency of a haplotype. For example, it would seem advantageous to have HLA molecules with non-overlapping binding specificities within a haplotype, as individuals expressing such an haplotype would present a diverse set of peptides from viruses and pathogenic bacteria on the cell surface. To test this hypothesis, we collect the proteome data from a set of common viruses, and estimate the total ligand repertoire of HLA class I haplotypes (HLA-A-B) using in silico predictions. We compare the size of these repertoires to the HLA haplotype frequencies reported in the National Marrow Donor Program (NMDP). We find that in most HLA-A and HLA-B pairs have fairly distinct binding motifs, and that the observed haplotypes do not contain HLA-A and -B molecules with more distinct binding motifs than random HLA-A and HLA-B pairs. In addition, the population frequency of a haplotype is not correlated to the distinctness of its HLA-A and HLA-B peptide binding motifs. These results suggest that there is a not a strong selection pressure on the haplotype level favoring haplotypes having HLA molecules with distinct binding motifs, which would result the largest possible presented peptide repertoires in the context of infectious diseases. PMID:24294213

  1. Sampling From the Proteome to the Human Leukocyte Antigen-DR (HLA-DR) Ligandome Proceeds Via High Specificity.

    Science.gov (United States)

    Mommen, Geert P M; Marino, Fabio; Meiring, Hugo D; Poelen, Martien C M; van Gaans-van den Brink, Jacqueline A M; Mohammed, Shabaz; Heck, Albert J R; van Els, Cécile A C M

    2016-04-01

    Comprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4(+)T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented peptides, using hybrid mass spectrometry-based peptide fragmentation techniques on a ligandome sample isolated from matured human monocyte-derived dendritic cells (DC). The reported data set constitutes nearly 14 thousand unique high-confident peptides,i.e.the largest single inventory of human DC derived HLA-DR ligands to date. From a technical viewpoint the most prominent finding is that no single peptide fragmentation technique could elucidate the majority of HLA-DR ligands, because of the wide range of physical chemical properties displayed by the HLA-DR ligandome. Our in-depth profiling allowed us to reveal a strikingly poor correlation between the source proteins identified in the HLA class II ligandome and the DC cellular proteome. Important selective sieving from the sampled proteome to the ligandome was evidenced by specificity in the sequences of the core regions both at their N- and C- termini, hence not only reflecting binding motifs but also dominant protease activity associated to the endolysosomal compartments. Moreover, we demonstrate that the HLA-DR ligandome reflects a surface representation of cell-compartments specific for biological events linked to the maturation of monocytes into antigen presenting cells. Our results present new perspectives into the complex nature of the HLA class II system and will aid future immunological studies in characterizing the full breadth of potential CD4(+)T cell epitopes relevant in health and disease. PMID:26764012

  2. Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human monoclonal HLA antibodies.

    Science.gov (United States)

    Eijsink, Chantal; Kester, Michel G D; Franke, Marry E I; Franken, Kees L M C; Heemskerk, Mirjam H M; Claas, Frans H J; Mulder, Arend

    2006-08-31

    The ability of tetrameric major histocompatibility complex (MHC) class I-peptide complexes (tetramers) to detect antigen-specific T lymphocyte responses has yielded significant information about the generation of in vivo immunity in numerous antigenic systems. Here we present a novel method for rapid validation of tetrameric HLA molecules based on the presence of allodeterminants. Human monoclonal antibodies (mAbs) recognizing polymorphic determinants on HLA class I were immobilized on polystyrene microparticles and used to probe the structural integrity of tetrameric HLA class I molecules by flow cytometry. A total of 22 tetramers, based on HLA-A1, A2, A3, A24, B7 and B8 were reactive with their counterpart mAbs, thus confirming their antigenic integrity. A positive outcome of this mAb test ensures that tetrameric HLA class I can be used with greater confidence in subsequent functional assays. PMID:16973172

  3. KIR3DL1 interaction with HLA-B27 is altered by ankylosing spondylitis associated ERAP1 and enhanced by MHC class I cross-linking.

    Science.gov (United States)

    Abdullah, Hasan; Zhang, Zhenbo; Yee, Kirby; Haroon, Nigil

    2015-01-01

    Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis of the spine and peripheral joints linked to the antigen presenting molecule HLA-B27. The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively. Dysfunction of ERAP1 is hypothesized to cause changes in expression of HLA-B27 classical (pHLA) and non-classical (FHC) conformers on antigen presenting cells (APCs), which interact with the natural killer (NK) cell receptor KIR3DL1. Dysregulation of this pathway may be pathogenic in AS. APC cell lines expressing HLA-B27 were found to inhibit cytokine production in KIR3DL1+ NK cells due to decreased APC-NK cell adhesion, and possibly activation of receptor down-regulation. Blocking pHLA and FHC reveals that both conformers inhibit cytokine production through KIR3DL1. KIR3DL1 affinity and HLA-B27 surface expression studies suggest that ERAP1 R528 and E730 expression protects from AS by generating sub-optimal pHLA, causing reduced KIR3DL1 affinity and weaker cytokine inhibition. Secondarily we observed that KIR3DL1 binding to C1R-B27 APCs is enhanced by blocking pHLA, but not FHC, raising the possibility that antibody mediated HLA-B27 cross-linking may be important in enhancing KIR3DL1+ NK cell function. This study establishes the role of both FHC and pHLA in modulating NK cell cytokine secretion and adhesion functions by interacting with KIR3DL1. This interaction varies depending on the AS association status of the ERAP1 variant expressed in APCs. Additionally antibody cross-linking of HLA-B27 enhances KIR3DL1 binding and as such could be an important pathogenic mechanism in AS. PMID:26321090

  4. Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I.

    Science.gov (United States)

    van den Boomen, D J H; Lehner, P J

    2015-12-01

    The human cytomegalovirus (HCMV) US2 and US11 gene products hijack mammalian ER-associated degradation (ERAD) to induce rapid degradation of major histocompatibility class I (MHC-I) molecules. The rate-limiting step in this pathway is thought to be the polyubiquitination of MHC-I by distinct host ERAD E3 ubiquitin ligases. TRC8 was identified as the ligase responsible for US2-mediated MHC-I degradation and shown to be required for the cleavage-dependent degradation of some tail-anchored proteins. In addition to MHC-I, plasma membrane profiling identified further immune receptors, which are also substrates for the US2/TRC8 complex. These include at least six α integrins, the coagulation factor thrombomodulin and the NK cell ligand CD112. US2's use of specific HCMV-encoded adaptors makes it an adaptable viral degradation hub. US11-mediated degradation is MHC-I-specific and genetic screens have identified TMEM129, an uncharacterised RING-C2 E3 ligase, as responsible for US11-mediated degradation. In a unique auto-regulatory loop, US11 readily responds to changes in cellular expression of MHC-I. Free US11 either rebinds more MHC-I or is itself degraded by the HRD1/SEL1L E3 ligase complex. While virally encoded US2 and US11 appropriate mammalian ERAD, the MHC-I complex also undergoes stringent cellular quality control and misfolded MHC-I is degraded by the HRD1/SEL1L complex. We discuss the identification and central role of E3 ubiquitin ligases in ER quality control and viral degradation of the MHC-I chain. PMID:26210183

  5. Human leukocyte antigen (HLA)-G during pregnancy part II

    DEFF Research Database (Denmark)

    Dahl, Mette; Klitkou, Louise; Christiansen, Ole B;

    2015-01-01

    Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent...... miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood...... plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing...

  6. Crystal structure of a murine α-class glutathione S-transferase involved in cellular defense against oxidative stress

    NARCIS (Netherlands)

    Krengel, Ute; Schröter, Klaus-Hasso; Hoier, Helga; Arkema, Anita; Kalk, Kor H.; Zimniak, Piotr; Dijkstra, Bauke W.

    1998-01-01

    Glutathione S-transferases (GSTs) are ubiquitous multifunctional enzymes which play a key role in cellular detoxification. The enzymes protect the cells against toxicants by conjugating them to glutathione. Recently, a novel subgroup of α-class GSTs has been identified with altered substrate specifi

  7. HIV control through a single nucleotide on the HLA-B locus

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; Harndahl, Mikkel; Leslie, Alasdair J;

    2012-01-01

    Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and...... strong linkage disequilibrium between HLA class I alleles complicates the discrimination of individual HLA allelic effects from those of other HLA and non-HLA alleles on the same haplotype. Here, we exploit an experiment of nature involving two recently diverged HLA alleles, HLA-B*42:01 and HLA-B*42......:02, which differ by only a single amino acid. Crucially, they occur primarily on identical HLA class I haplotypes and, as Bw6 alleles, do not act as NK cell ligands and are therefore largely unconfounded by other genetic factors. We show that in an outbred cohort (n = 2,093) of HIV C...

  8. Differential clade-specific HLA-B*3501 association with HIV-1 disease outcome is linked to immunogenicity of a single Gag epitope

    DEFF Research Database (Denmark)

    Matthews, Philippa C; Koyanagi, Madoka; Kløverpris, Henrik N;

    2012-01-01

    The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-...

  9. Association between Alu insertion polymorphisms and HLA class T alleles in Chinese Lisu and Nu ethnic populations%中国傈僳族和怒族群体人类白细胞抗原Ⅰ类基因区Alu插入多态性研究

    Institute of Scientific and Technical Information of China (English)

    董兆梅; 姚宇峰; 史磊; 陶玉芬; 林克勤; 黄小琴; 杨昭庆; 褚嘉祐; 史荔

    2012-01-01

    Objective To investigate the frequencies of HLA-Alu repeat polymorphisms (AluMICB,AluTF,AluHJ,AluHG and AluHF) in Chinese Lisu and Nu ethnic populations.Methods The frequencies of HLA-Alu repeat polymorphisms in above populations were determined with polymerase chain reaction (PCR).The associations between HLA-Alu repeat polymorphisms and HLA-A,HLA-B and HLA-C alleles were also analyzed.Phylogenetic trees were constructed with genetic distance calculated from the frequencies of HLA-Alu repeat polymorphisms.Results Frequencies of AluTF * 2 and AluHF * 2 were different between the two populations (P<0.05),while those of other three insertions were similar.The strength of association between HLA-Alus and HLA alleles were different (P<0.05) in the two populations.Although AluMICB * 2 were associated with HLA-B* 56:01 in both populations,the association was stronger in Lisu population (74.0%) but moderate in Nu population (30.7%).HLA-Alus were associated with particular HLA subtypes,e.g.,AluHG * 2 with certain HLA-A * 02 subtypes.By phylogenetic analysis,Lisu and Nu were clustered together with southern Chinese and Thai populations.Conclusion The distribution of HLA-Alus and the strength of associations between HLA-Alus and HLA class I alleles have varied between the two populations.Study of this association may facilitate identification of origins,evolution,progenitor haplotypes and recombination within the HLA class I region.%目的 研究中国两个隔离群体(傈僳族和怒族)人类白细胞抗原(human leukocyte antigen,HLA)Ⅰ类基因区域内5个HLA-Alu插入多态性(AluMICB、AluTF、AluHJ、AluHG和AluHF)的分布特征.方法 应用聚合酶链反应技术对中国两个隔离群体傈僳族(107人)和怒族(104人)进行HLA-Alu多态性分型.结合HLA基因分型数据,分析这两个群体中HLA-Alu插入与HLA-A、HLA-B和HLA-C基因的关系.根据HLA-Alu频率计算各群体间遗传距离,构建系统进化树.结果 AluTF和AluHF插入

  10. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups (Retracted article. See vol. 118, pg. 5211, 2011)

    NARCIS (Netherlands)

    Huang, Xin; Kushekhar, Kushi; Nolte, Ilja; Kooistra, Wierd; Visser, Lydia; Bouwman, Ilby; Kouprie, Niels; van Imhoff, Gustaaf; Olver, Bianca; Houlston, Richard S.; Poppema, Sibrand; Diepstra, Arjan; Hepkema, Bouke; van den Berg, Anke; Veenstra, R.

    2011-01-01

    The pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients and more than 5000 controls using a PCR-based sequence-specific olig

  11. NK cell activity during human cytomegalovirus ingection is dominated by US2-11mediated HLA class I down-regulation

    Czech Academy of Sciences Publication Activity Database

    Falk, C. S.; Mach, M.; Schendel, D. J.; Weiss, E. H.; Hilgert, Ivan; Hahn, G.

    2002-01-01

    Roč. 169, č. 6 (2002), s. 3257-3266. ISSN 0022-1767 Institutional research plan: CEZ:AV0Z5052915 Keywords : NK cell * cytomegalovirus * HLA-E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.014, year: 2002

  12. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBVI Hodgkin lymphoma

    NARCIS (Netherlands)

    Niens, Marijke; Jarreft, Ruth F.; Hepkema, Bouke; Nolte, Ilja M.; Diepstra, Arjan; Platteel, Mathieu; Kouprie, Niels; Delury, Craig P.; Gallagher, Alice; Visser, Lydia; Poppema, Sibrand; te Meerman, Gerard J.; Van den Berg, Anke

    2007-01-01

    Previous studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the

  13. HLA-G molecule as inductor of immunotolerance

    International Nuclear Information System (INIS)

    HLA-G are molecules are (non-classic) class I antigens from main histocompatibility system. There are sis isoforms of HLA-G antigen codifying four proteins united to a membrane (HLA-G1, HLA-G2, HLA-G3, HLA-G4), and three soluble isoforms (HLA-G5, HLA-G6, HLA-G7). The first ones are expressed in cells of placental extravillous cytotrophoblast (Langhans' layer), amnios epithelial cells, fetal endothelial cells, mesenchymal macrophages of chorionic villi, and in epithelial cells of thymus medulla; the second ones in amniotic fluid, in maternal peripheral blood and that of the umbilical cord. There was a HLA-G expression in some types of tumors, stroma cells under inflammation conditions, virus-infected cells and in serum of transplant patients. There are strong evidences of HLA-G molecules role in tolerance induction to these physiological and pathological situations through suppression of lithic activity of NK cells and of cytotoxic T lymphocytes. This knowledge may be very useful in future therapeutical management of these entities as well as to favor the success of tissue and organ transplant

  14. Binding of actin by neutrophil (PMN) C3b receptor (CR1), iC3b receptor (CR3) and Fc receptor (FcR), but not by HLA class I or erythrocyte (E) CR1

    International Nuclear Information System (INIS)

    An association of PMN CR1 with actin-containing cytoskeleton has been suggested by the subplasmalemmal accumulation of actin and myosin with CR1 caps, and by the binding of cross-linked CR1 to detergent-insoluble cytoskeleton under conditions that maintain the stability of F-actin. To assess more directly the interaction of CR1 with actin, PMN detergent lysates were absorbed with the Sepharose-bound monoclonal antibodies YZ-1 anti-CR1, W6/32 anti-HLA Class I or UPC-10 anti-levan. CR1 from E lysates also was immunoadsorbed. The Sepharose beads bearing immobilized membrane proteins were incubated with 125I-labeled rabbit alveolar macrophage actin in isotonic buffer containing 0.5% NP-40, washed and assayed. PMN CR1, PMN HLA and E CR1 bound 6.7-14.2, 2.1-3.3, and 1.5-4.3 times as much actin as did the control UPC-10 beads. PMN lysates also were absorbed with immobilized 3G8.10 anti-FcR, LM2/1 anti-CR3, Yz-1 and W6/32 and the complexes were assessed for binding of 125I actin. FcR, CR3 and CR1 bound 3.4, 2.1, and 2.3 times as much actin as did control beads; HLA did not specifically bind actin. Thus, the capacity of PMN membrane proteins to bind actin correlates with their endocytic function, and CR1 exhibits cell-specific differential binding of actin

  15. HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Hylenius, Sine; Rørbye, Christina;

    2003-01-01

    During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship...... between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain...... HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed at a...

  16. Molecular analysis of polimorphisms in HLA-CLASS II DRB1* and IL7Rα possibly associated with multiple sclerosis susceptibility in a population sample of Rio de Janeiro

    Directory of Open Access Journals (Sweden)

    André Luis dos Santos Figueiredo

    2014-06-01

    Full Text Available Multiple sclerosis (MS is an inflammatory and degenerative disease of the central nervous system (CNS that affects mainly young adults. MS seems to be a polygenic and multifactorial disease, and genetic susceptibility has been associated mainly with the major histocompatibility complex (MHC, which in humans is the human leukocyte antigen (HLA. Among non-HLA genes is the alpha chain of interleukin 7 receptor gene (IL7Rα at the 5p12-14 locus, also known as CD127. The aim of this study was to evaluate the correlations between polymorphism in the IL7Rα (rs6897932C gene, HLA-class II DRB1* haplotypes and susceptibility to multiple sclerosis in patients with Recurrent Remitting form (RRMS. METHOD: In this study, peripheral blood samples were taken from 50 patients diagnosed using the diagnostic criteria for MS according to Polman (MacDonald et al (2011. The patients were monitored at the Clinic of Neurology, Hospital Universitário Clementino Fraga Filho, along with 100 healthy control subjects matched for ancestry, sex and age. After DNA extraction by organic method, polymorphism +244 *C (rs6897932 was assessed by PCR followed by capillary electrophoresis on the ABI PRISM® 3500 Genetic Analyzer (Applied Biosystems, USA platform. RESULTS: The results indicated a significant association between the CC haplotype and RRMS (p=0.02 , OR=2.14, as well as an association between the *C allele (CC and CT and RRMS (p=0.042, OR=2.15. The same C allele was more frequent in the sample, both in patients (0.82, and in the control group (0.71. The sample, control group and patients included, was in Hardy- Weinberg equilibrium. The correlation between the presence of the CC genotype and HLA-DRB1* 15:01 was significant (OR=3.6, p=0.034. CONCLUSION: These results reinforce the polygenic/multifactorial characteristic or genetic heterogeneity of MS, indicating a relationship between putative polymorphism +244*C (CC genotype in the IL7Rα gene and susceptibility to MS

  17. HLA-E polymorphism and soluble HLA-E plasma levels in chronic hepatitis B patients.

    Science.gov (United States)

    Zidi, I; Laaribi, A B; Bortolotti, D; Belhadj, M; Mehri, A; Yahia, H B; Babay, W; Chaouch, H; Zidi, N; Letaief, A; Yacoub, S; Boukadida, J; Di Luca, D; Hannachi, N; Rizzo, R

    2016-03-01

    Chronic hepatitis B virus (HBV) infection occurs in association to a deregulation of immune system. Human leukocyte antigen E (HLA-E) is an immune-tolerant nonclassical HLA class I molecule that could be involved in HBV progression. To measure soluble (s) HLA-E in patients with chronic HBV hepatitis (CHB). We tested the potential association of HLA-E*01:01/01:03 A > G gene polymorphism to CHB. Our cohort consisted of 93 Tunisian CHB patients (stratified in CHB with high HBV DNA levels and CHB with low HBV DNA levels) and 245 healthy donors. Plasma sHLA-E was determined using enzyme-linked immunosorbent assay (ELISA). Genotyping was performed using polymerase chain reaction sequence-specific primer. No association between HLA-E*01:01/01:03 A > G polymorphism and HBV DNA levels in CHB patients was found. G/G genotype is less frequent in CHB patients without significance. sHLA-E is significantly enhanced in CHB patients compared with healthy controls (P = 0.0017). Stratification according to HBV DNA levels showed that CHB patients with low HBV DNA levels have higher sHLA-E levels compared with CHB patients with high HBV DNA levels. CHB patients with G/G genotype have enhanced sHLA-E levels compared with other genotypes (P = 0.037). This significant difference is maintained only for CHB women concerning G/G genotypes (P = 0.042). Finally, we reported enhanced sHLA-E in CHB patients with advanced stages of fibrosis (P = 0.032). We demonstrate, for the first time, the association of sHLA-E to CHB. Owing to the positive correlation of HLA-E*01:01/01:03 A > G polymorphism and the association of sHLA-E to advanced fibrosis stages, HLA-E could be a powerful predictor for CHB progression. Further investigations will be required to substantiate HLA-E role as a putative clinical biomarker of CHB. PMID:26956431

  18. Peptide binding predictions for HLA DR, DP and DQ molecules

    DEFF Research Database (Denmark)

    Wang, P.; Sidney, J.; Kim, Y.;

    2010-01-01

    BACKGROUND: MHC class II binding predictions are widely used to identify epitope candidates in infectious agents, allergens, cancer and autoantigens. The vast majority of prediction algorithms for human MHC class II to date have targeted HLA molecules encoded in the DR locus. This reflects a...... significant gap in knowledge as HLA DP and DQ molecules are presumably equally important, and have only been studied less because they are more difficult to handle experimentally. RESULTS: In this study, we aimed to narrow this gap by providing a large scale dataset of over 17,000 HLA-peptide binding...... affinities for a set of 11 HLA DP and DQ alleles. We also expanded our dataset for HLA DR alleles resulting in a total of 40,000 MHC class II binding affinities covering 26 allelic variants. Utilizing this dataset, we generated prediction tools utilizing several machine learning algorithms and evaluated...

  19. Evaluation of Association Between HLA Class II DR4–DQ8 Haplotype and Type I Diabetes Mellitus in Children of East Azerbaijan State of Iran

    Directory of Open Access Journals (Sweden)

    Nasrin Sohrabi

    2015-04-01

    Full Text Available Purpose: Association between HLA-DR4–DQ8 haplotype and type 1 Diabetes Mellitus (DM-1A was investigated in children of East Azerbaijan state of Iran because such an association has not been previously studied in this population. Methods: HLA-typing was performed by polymerase chain reaction sequence-specific priming. For haplotype analysis, the logistic regression model was performed. Results: Of the three investigated alleles, the frequency of DRB1*0401 was significantly higher among patients compared with that in healthy subjects (76.74% vs. 23.26%. Conclusion: The findings of the current study are consistent with those of previous studies and show that DRB1*0401 is associated with DM-1A; the frequencies of the two other alleles were also higher among patients, although the differences were not statistically significant. Two haplotypes associated with these alleles were also surveyed, and DRB1*0401−-DQA1*0301−, and DRB1*0401−-DQA1*0301−-DQB1*0302− were the most frequent haplotypes among the patient group.

  20. High frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.

    Directory of Open Access Journals (Sweden)

    Kamini Gounder

    Full Text Available In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II] and at one-year post infection respectively were generated. Six of 22 (27% individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39. At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3% comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses.

  1. HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Rizzo, R; Hviid, T V F; Govoni, M;

    2008-01-01

    increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results...... antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The...... insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian...

  2. The Potential of HLA-G-Bearing Extracellular Vesicles as a Future Element in HLA-G Immune Biology.

    Science.gov (United States)

    Rebmann, Vera; König, Lisa; Nardi, Fabiola da Silva; Wagner, Bettina; Manvailer, Luis Felipe Santos; Horn, Peter A

    2016-01-01

    The HLA-G molecule is a member of the non-classical HLA class I family. Its surface expression is physiologically restricted to the maternal-fetal interface and to immune privileged adult tissues. Despite the restricted tissue expression, HLA-G is detectable in body fluids as secreted soluble molecules. A unique feature of HLA-G is the structural diversity as surface expressed and as secreted molecules. Secreted HLA-G can be found in various body fluids either as free soluble HLA-G or as part of extracellular vesicles (EVs), which are composed of various antigens/ligands/receptors, bioactive lipids, cytokines, growth factors, and genetic information, such as mRNA and microRNA. Functionally, HLA-G and its secreted forms are considered to play a crucial role in the network of immune-regulatory tolerance mechanisms, preferentially interacting with the cognate inhibitory receptors LILRB1 and LILRB2. The HLA-G mediated tolerance is described in processes of pregnancy, inflammation, and cancer. However, almost all functional and clinical implications of HLA-G in vivo and in vitro have been established based on simple single ligand/receptor interactions at the cell surface, whereas HLA-G-bearing EVs were in minor research focus. Indeed, cytotrophoblast cells, mesenchymal stem cells, and cancer cells were recently described to secrete HLA-G-bearing EVs, displaying immunosuppressive effects and modulating the tumor microenvironment. However, numerous functional and clinical open questions persist. Here, we (i) introduce basic aspects of EVs biology, (ii) summarize the functional knowledge, clinical implications and open questions of HLA-G-bearing EVs, and (iii) discuss HLA-G-bearing EVs as a future element in HLA-G biology. PMID:27199995

  3. Autoinflammation and HLA-B27: Beyond Antigen Presentation.

    Science.gov (United States)

    Sibley, Cailin H

    2016-08-01

    HLA-B27 associated disorders comprise a group of inflammatory conditions which have in common an association with the HLA class I molecule, HLA-B27. Given this association, these diseases are classically considered disorders of adaptive immunity. However, mounting data are challenging this assumption and confirming that innate immunity plays a more prominent role in pathogenesis than previously suspected. In this review, the concept of autoinflammation is discussed and evidence is presented from human and animal models to support a key role for innate immunity in HLA-B27 associated disorders. PMID:27229619

  4. Human leukocyte antigen (HLA)-G during pregnancy part I

    DEFF Research Database (Denmark)

    Klitkou, Louise; Dahl, Mette; Hviid, Thomas Vauvert F;

    2015-01-01

    Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on trophoblast cells and has been proposed to have immunomodulatory functions during pregnancy. Soluble HLA-G1 (sHLA-G1) can be generated by the shedding of membrane-bound HLA-G molecules; however......, three soluble isoforms also exist (HLA-G5 to -G6). During pregnancy, it is unknown whether there is a correlation between sHLA-G levels in maternal and fetal blood. In 246 pregnancies, we have measured the levels of sHLA-G1/-G5 in maternal blood plasma samples from gestational week 20 (GW20) and at term......, as well as in umbilical cord blood samples. Soluble HLA-G levels declined by 38.4% in maternal blood from GW20 to term, and sHLA-G levels were significantly lower in maternal blood at term than in GW20 (P<0.001). At term, the sHLA-G levels were significantly higher in maternal blood than in umbilical...

  5. Restriction fragment length polymorphism of the HLA-DP subregion and correlations to HLA-DP phenotypes

    DEFF Research Database (Denmark)

    Hyldig-Nielsen, J J; Morling, Niels; Ødum, Niels;

    1987-01-01

    The restriction fragment length polymorphism (RFLP) of the class II HLA-DP subregion of the major histocompatibility complex (MHC) of humans has been unraveled by Southern blotting using DP alpha and DP beta probes in a study of 46 unrelated individuals with known HLA-DP types. Contrary to earlier...

  6. HLA-G Molecules in Autoimmune Diseases and Infections

    Science.gov (United States)

    Rizzo, Roberta; Bortolotti, Daria; Bolzani, Silvia; Fainardi, Enrico

    2014-01-01

    Human leukocyte antigen (HLA)-G molecule, a non-classical HLA-Ib molecule, is less polymorphic when compared to classical HLA class I molecules. Human leukocyte antigen-G (HLA-G) was first detected on cytotrophoblast cells at the feto-maternal interface but its expression is prevalent during viral infections and several autoimmune diseases. HLA-G gene is characterized by polymorphisms at the 3′ un-translated region and 5′ upstream regulatory region that regulate its expression and are associated with autoimmune diseases and viral infection susceptibility, creating an unbalanced and pathologic environment. This review focuses on the role of HLA-G genetic polymorphisms, mRNA, and protein expression in autoimmune conditions and viral infections. PMID:25477881

  7. HLA-G polymorphisms in couples with recurrent spontaneous abortions

    DEFF Research Database (Denmark)

    Hviid, T V; Hylenius, S; Hoegh, A M;

    2002-01-01

    The etiology of a fraction of recurrent spontaneous abortions (RSA) may involve immunological mechanisms. Aberrant profiles of Th1 and Th2 cytokines have been observed which are not present in uncomplicated pregnancies. Studies of classical HLA class I and II antigens in relation to RSA have not...... been conclusive. Furthermore, these antigens are not expressed in the placenta with the exception of HLA-C. However, HLA-G is expressed on especially invasive cytotrophoblasts and exists in both membrane and soluble forms. HLA-G may be involved in materno-fetal tolerance. Therefore, 61 RSA couples...... (with three or more spontaneous abortions) and 47 fertile control couples were HLA-G genotyped by direct DNA sequencing and analyzed for specific polymorphisms. No statistically significant differences were observed in the distribution of HLA-G alleles between controls and RSA couples, however, 15% of...

  8. MULTIPRED2: A computational system for large-scale identification of peptides predicted to bind to HLA supertypes and alleles

    DEFF Research Database (Denmark)

    Zhang, Guang Lan; DeLuca, David S.; Keskin, Derin B.;

    2011-01-01

    MULTIPRED2 is a computational system for facile prediction of peptide binding to multiple alleles belonging to human leukocyte antigen (HLA) class I and class II DR molecules. It enables prediction of peptide binding to products of individual HLA alleles, combination of alleles, or HLA supertypes...

  9. Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities

    DEFF Research Database (Denmark)

    Southwood, Scott; Solomon, Christopher; Hoof, Ilka;

    2011-01-01

    rhesus macaques’ major histocompatibility complex (MHC) for composition and function should facilitate greater utilization of the species. Previous studies have demonstrated that Chinese-origin M. mulatta (Mamu) class I alleles are more polymorphic than their Indian counterparts, perhaps inferring a...... populations. In this study, we have characterized two additional alleles expressed with high frequency in Chinese rhesus macaques, Mamu-A1*02601 and Mamu-B*08301. Upon the development of MHC–peptide-binding assays and definition of their associated motifs, we reveal that these Mamu alleles share peptide...

  10. Lassa fever virus peptides predicted by computational analysis induce epitope-specific cytotoxic-T-lymphocyte responses in HLA-A2.1 transgenic mice.

    Science.gov (United States)

    Boesen, Agnieszka; Sundar, Krishnan; Coico, Richard

    2005-10-01

    Lassa fever is a hemorrhagic disease caused by Lassa fever virus (LV). Although the precise host defense mechanism(s) that affords protection against LV is not completely understood, cellular immunity mediated by cytotoxic T lymphocytes (CTLs) plays a pivotal role in controlling viral replication and LV infection. To date, there have been no reports mapping major histocompatibility complex (MHC) class I-binding CTL epitopes for LV. Using computer-assisted algorithms, we identified five HLA-A2.1-binding peptides of LV glycoprotein (GP) and two peptides from LV nucleoprotein (NP). Synthesized peptides were examined for their ability to bind to MHC class I molecules using a flow cytometric assay that measures peptide stabilization of class I. Three of the LV-GP peptides tested (LLGTFTWTL, SLYKGVYEL, and YLISIFLHL) stabilized HLA-A2. The LV-NP peptides tested failed to stabilize this HLA-A2. We then investigated the ability of the HLA-A2-binding LV-GP peptides to generate peptide-specific CTLs in HLA-A2.1 transgenic mice. Functional assays used to confirm CTL activation included gamma interferon enzyme-linked immunospot (ELISPOT) assays and intracellular cytokine staining of CD8+ T cells from peptide-primed mice. CTL assays were also performed to verify the cytolytic activity of peptide-pulsed target cells. Each of the LV-GP peptides induced CTL responses in HLA-A2-transgenic mice. MHC class I tetramers prepared using one LV-GP peptide that showed the highest cytolytic index (LLGTFTWTL) confirmed that peptide-binding CD8+ T cells were present in pooled lymphocytes harvested from peptide-primed mice. These findings provide direct evidence for the existence of LV-derived GP epitopes that may be useful in the development of protective immunogens for this hemorrhagic virus. PMID:16210487

  11. Lassa Fever Virus Peptides Predicted by Computational Analysis Induce Epitope-Specific Cytotoxic-T-Lymphocyte Responses in HLA-A2.1 Transgenic Mice

    Science.gov (United States)

    Boesen, Agnieszka; Sundar, Krishnan; Coico, Richard

    2005-01-01

    Lassa fever is a hemorrhagic disease caused by Lassa fever virus (LV). Although the precise host defense mechanism(s) that affords protection against LV is not completely understood, cellular immunity mediated by cytotoxic T lymphocytes (CTLs) plays a pivotal role in controlling viral replication and LV infection. To date, there have been no reports mapping major histocompatibility complex (MHC) class I-binding CTL epitopes for LV. Using computer-assisted algorithms, we identified five HLA-A2.1-binding peptides of LV glycoprotein (GP) and two peptides from LV nucleoprotein (NP). Synthesized peptides were examined for their ability to bind to MHC class I molecules using a flow cytometric assay that measures peptide stabilization of class I. Three of the LV-GP peptides tested (LLGTFTWTL, SLYKGVYEL, and YLISIFLHL) stabilized HLA-A2. The LV-NP peptides tested failed to stabilize this HLA-A2. We then investigated the ability of the HLA-A2-binding LV-GP peptides to generate peptide-specific CTLs in HLA-A2.1 transgenic mice. Functional assays used to confirm CTL activation included gamma interferon enzyme-linked immunospot (ELISPOT) assays and intracellular cytokine staining of CD8+ T cells from peptide-primed mice. CTL assays were also performed to verify the cytolytic activity of peptide-pulsed target cells. Each of the LV-GP peptides induced CTL responses in HLA-A2-transgenic mice. MHC class I tetramers prepared using one LV-GP peptide that showed the highest cytolytic index (LLGTFTWTL) confirmed that peptide-binding CD8+ T cells were present in pooled lymphocytes harvested from peptide-primed mice. These findings provide direct evidence for the existence of LV-derived GP epitopes that may be useful in the development of protective immunogens for this hemorrhagic virus. PMID:16210487

  12. Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I

    OpenAIRE

    van den Boomen, D.J.H.; Lehner, P. J.

    2015-01-01

    The human cytomegalovirus (HCMV) US2 and US11 gene products hijack mammalian ER-associated degradation (ERAD) to induce rapid degradation of major histocompatibility class I (MHC-I) molecules. The rate-limiting step in this pathway is thought to be the polyubiquitination of MHC-I by distinct host ERAD E3 ubiquitin ligases. TRC8 was identified as the ligase responsible for US2-mediated MHC-I degradation and shown to be required for the cleavage-dependent degradation of some tail-anchored prote...

  13. Lassa Fever Virus Peptides Predicted by Computational Analysis Induce Epitope-Specific Cytotoxic-T-Lymphocyte Responses in HLA-A2.1 Transgenic Mice

    OpenAIRE

    Boesen, Agnieszka; Sundar, Krishnan; Coico, Richard

    2005-01-01

    Lassa fever is a hemorrhagic disease caused by Lassa fever virus (LV). Although the precise host defense mechanism(s) that affords protection against LV is not completely understood, cellular immunity mediated by cytotoxic T lymphocytes (CTLs) plays a pivotal role in controlling viral replication and LV infection. To date, there have been no reports mapping major histocompatibility complex (MHC) class I-binding CTL epitopes for LV. Using computer-assisted algorithms, we identified five HLA-A2...

  14. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2014-05-01

    Full Text Available Bacillus anthracis produces a binary toxin composed of protective antigen (PA and one of two subunits, lethal factor (LF or edema factor (EF. Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  15. IgE production after antigen-specific and cognate activation of HLA-DPw4-restricted T-cell clones, by 78% of randomly selected B-cell donors

    NARCIS (Netherlands)

    Baselmans, PJ; Pollabauer, EM; van Reijsen, FC; Heystek, HC; Hren, A; Stumptner, P; Tilanus, MGJ; Vooijs, WC; Mudde, GC

    2000-01-01

    The frequency of expression of the MHC class II antigen, HLA-DPw4, in the caucasoid population is approximately 78%, and is unmatched by phenotypic frequencies of other HLA class II molecules. Here we describe three human Der-P1-specific T-cell clones (TCC), restricted by the HLA-DPw4-variant HLA-DP

  16. Antagonist HIV-1 Gag Peptides Induce Structural Changes in HLA B8

    OpenAIRE

    Reid, Scott W.; McAdam, Steve; Smith, Kathrine J.; Klenerman, Paul; O'Callaghan, Chris A.; Harlos, Karl; Jakobsen, Bent K.; McMichael, Andrew J.; Bell, John I; Stuart, David I.; Jones, E. Yvonne

    1996-01-01

    In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959–968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541–1550). In one example, lysis of antig...

  17. Immunomodulation of classical and non-classical HLA molecules by ionizing radiation.

    Science.gov (United States)

    Gallegos, Cristina E; Michelin, Severino; Dubner, Diana; Carosella, Edgardo D

    2016-05-01

    Radiotherapy has been employed for the treatment of oncological patients for nearly a century, and together with surgery and chemotherapy, radiation oncology constitutes one of the three pillars of cancer therapy. Ionizing radiation has complex effects on neoplastic cells and on tumor microenvironment: beyond its action as a direct cytotoxic agent, tumor irradiation triggers a series of alterations in tumoral cells, which includes the de novo synthesis of particular proteins and the up/down-regulation of cell surface molecules. Additionally, ionizing radiation may induce the release of "danger signals" which may, in turn lead to cellular and molecular responses by the immune system. This immunomodulatory action of ionizing radiation highlights the importance of the combined use (radiotherapy plus immunotherapy) for cancer healing. Major histocompatibility complex antigens (also called Human Leukocyte Antigens, HLA in humans) are one of those molecules whose expression is modulated after irradiation. This review summarizes the modulatory properties of ionizing radiation on the expression of HLA class I (classical and non-classical) and class II molecules, with special emphasis in non-classical HLA-I molecules. PMID:27113815

  18. A novel method to measure HLA-DM-susceptibility of peptides bound to MHC class II molecules based on peptide binding competition assay and differential IC(50) determination.

    Science.gov (United States)

    Yin, Liusong; Stern, Lawrence J

    2014-04-01

    HLA-DM (DM) functions as a peptide editor that mediates the exchange of peptides loaded onto MHCII molecules by accelerating peptide dissociation and association kinetics. The relative DM-susceptibility of peptides bound to MHCII molecules correlates with antigen presentation and immunodominance hierarchy, and measurement of DM-susceptibility has been a key effort in this field. Current assays of DM-susceptibility, based on differential peptide dissociation rates measured for individually labeled peptides over a long time base, are difficult and cumbersome. Here, we present a novel method to measure DM-susceptibility based on peptide binding competition assays performed in the presence and absence of DM, reported as a delta-IC(50) (change in 50% inhibition concentration) value. We simulated binding competition reactions of peptides with various intrinsic and DM-catalyzed kinetic parameters and found that under a wide range of conditions the delta-IC(50) value is highly correlated with DM-susceptibility as measured in off-rate assay. We confirmed experimentally that DM-susceptibility measured by delta-IC(50) is comparable to that measured by traditional off-rate assay for peptides with known DM-susceptibility hierarchy. The major advantage of this method is that it allows simple, fast and high throughput measurement of DM-susceptibility for a large set of unlabeled peptides in studies of the mechanism of DM action and for identification of CD4+ T cell epitopes. PMID:24583195

  19. Transfusion Related Acute Lung Injury (TRALI Caused by Red Blood Cell Transfusion Involving Residual Plasma Anti-HLA Antibodies: A report on two Cases and General Considerations

    Directory of Open Access Journals (Sweden)

    Olivier Garraud

    2005-01-01

    Full Text Available TRALI is considered a serious hazard among immune complications of blood transfusion and its occurrence is admitted to be globally underestimated. Each type of blood product is likely to cause TRALI. We report here on two consecutive observations of TRALI caused by red blood cell concentrates, in which anti-HLA class I and class II antibodies resulting from post-gravitational allo-immunization were evidenced in donors. HLA class I and II antigenic community between recipients and donors' husbands were found and strong reacting IgG antibodies directed at several of those common antigens were detected in the donors' serum. Both donors had more than 3 pregnancies, raising the issue of blood donor selection or of plasma reduction for cellular products.

  20. Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes.

    Science.gov (United States)

    Smith, Wade P; Vu, Quyen; Li, Shuying Sue; Hansen, John A; Zhao, Lue Ping; Geraghty, Daniel E

    2006-05-01

    We carried out a resequencing project that examined 552 kb of sequence from each of 46 individual HLA haplotypes representing a diversity of HLA allele types, generating nearly 27 Mb of fully phased genomic sequence. Haplotype blocks were defined extending from telomeric of HLA-F to centromeric of HLA-DP including in total 5186 MHC SNPs. To investigate basic questions about the evolutionary origin of common HLA haplotypes, and to obtain an estimate of rare variation in the MHC, we similarly examined two additional sets of samples. In 19 independent HLA-A1, B8, DR3 chromosomes, the most common HLA haplotype in Northern European Caucasians, variation was found at 11 SNP positions in the 3600-kb region from HLA-A to DR. Partial resequencing of 282 individuals in the gene-dense class III region identified significant variability beyond what could have been detected by linkage to common SNPs. PMID:16434165

  1. Two Cases of Transfusion-related Acute Lung Injury Triggered by HLA and Anti-HLA Antibody Reaction

    OpenAIRE

    Lee, Ji Hyun; Kang, Eun-Suk; Kim, Dae-Won

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary edema, which develops during or within 6 hr of transfusion. Major pathogenesis of TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% ...

  2. The distribution of KIR-HLA functional blocks is different from north to south of Italy.

    Science.gov (United States)

    Fasano, M E; Rendine, S; Pasi, A; Bontadini, A; Cosentini, E; Carcassi, C; Capittini, C; Cornacchini, G; Espadas de Arias, A; Garbarino, L; Carella, G; Mariotti, M L; Mele, L; Miotti, V; Moscetti, A; Nesci, S; Ozzella, G; Piancatelli, D; Porfirio, B; Riva, M R; Romeo, G; Tagliaferri, C; Lombardo, C; Testi, M; Amoroso, A; Martinetti, M

    2014-03-01

    The killer cell immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA) interaction represents an example of genetic epistasis, where the concomitant presence of specific genes or alleles encoding receptor-ligand units is necessary for the activity of natural killer (NK) cells. Although KIR and HLA genes segregate independently, they co-evolved under environmental pressures to maintain particular KIR-HLA functional blocks for species survival. We investigated, in 270 Italian healthy individuals, the distribution of KIR and HLA polymorphisms in three climatic areas (from cold north to warm south), to verify their possible geographical stratification. We analyzed the presence of 13 KIR genes and genotyped KIR ligands belonging to HLA class I: HLA-C, HLA-B and HLA-A. We did not observe any genetic stratification for KIR genes and HLA-C ligands in Italy. By contrast, in a north-to-south direction, we found a decreasing trend for the HLA-A3 and HLA-A11 ligands (P = 0.012) and an increasing trend for the HLA-B ligands carrying the Bw4 epitope (P = 0.0003) and the Bw4 Ile80 epitope (P = 0.0005). The HLA-A and HLA-B KIR ligands were in negative linkage disequilibrium (correlation coefficient -0.1211), possibly as a consequence of their similar function in inhibiting NK cells. The distribution of the KIR-HLA functional blocks was different along Italy, as we observed a north-to-south ascending trend for KIR3DL1, when coupled with HLA-B Bw4 ligands (P = 0.0067) and with HLA-B Bw4 Ile80 (P = 0.0027), and a descending trend for KIR3DL2 when coupled with HLA-A3 and HLA-A11 ligands (P = 0.0044). Overall, people from South Italy preferentially use the KIR3DL1-HLA-B Bw4 functional unit, while those from the North Italy equally use both the KIR3DL2-HLA-A3/A11 and the KIR3DL1-HLA-B Bw4 functional units to fight infections. Thus, only KIR3DL receptors, which exert the unique role of microbial sensors through the specific D0 domain, and their cognate

  3. Molecular definition of a polymorphic antigen (LA45) of free HLA-A and -B heavy chains found on the surfaces of activated B and T cells.

    Science.gov (United States)

    Madrigal, J A; Belich, M P; Benjamin, R J; Little, A M; Hildebrand, W H; Mann, D L; Parham, P

    1991-11-01

    A monomoprhic monoclonal antibody (LA45 antibody) reactive with "a new activation-induced surface structure on human T lymphocytes" (LA45 antigen) that resembled free class I heavy chains has recently been described (Schnabl, E., H. Stockinger, O. Majdic, H. Gaugitsch, I.J.D. Lindley, D. Maurer, A. Hajek-Rosenmayr, and W. Knapp. 1990. J. Exp. Med. 171:1431). This antibody was used to clone a class I-like heavy chain (LA45 gene) from the HUT 102 tumor cell, which paradoxically did not give rise to the LA45 antigen on transfection into monkey COS cells. We show here that the LA45 gene is HLA-Aw66.2, a previously uncharacterized allele of the HLA-A locus. The previously determined LA45 sequence differs from that of HLA-Aw66.2, from HUT 102, and the CR-B B cell line derived from the same individual as HUT 102 by substitution of tryptophan for serine at position 4 in the alpha 1 domain. Transfection of HLA-Aw66.2, and of a mutant of this gene with serine 4 substituted for tryptophan, into a human B cell line (C1R) both resulted in expression of the LA45 epitope. Furthermore, we find expression of the LA45 epitope on Epstein Barr virus-transformed B cell lines as well as lectin-activated T cells, but not on long-term T cell lines or unstimulated peripheral blood T cells. The specificity of the LA45 antibody is polymorphic and the presence of the LA45 epitope is precisely correlated with the sequence arginine, asparagine (RN) at residues 62 and 63 of the helix of the alpha 1 domain. The LA45 epitope is broadly distributed, being associated with half the alleles of both HLA-A and -B loci but none of the HLA-C locus. All the results are consistent with the presence of pools of free HLA-A and -B heavy chains at the surfaces of certain cell types but not others. Such molecules are probably responsible for the HLA-associated class I alloantigens of lectin-activated T cells. We hypothesize the free heavy chains result from dissociation of beta 2-microglobulin from

  4. Human monoclonal antibodies as a tool for the detection of HLA class I allele-specific expression loss in head-and-neck squamous cell carcinoma and corresponding lymph node metastases

    NARCIS (Netherlands)

    Koene, Geert; Mulder, Arend; van der Ven, Kevin; Eijsink, Chantal; Franke, Marry; Slootweg, Piet; Claas, Frans; Tilanus, Marcel

    2006-01-01

    Human leukocyte antigen (HLA) expression is important for the elimination of tumor cells by the immune system and immunotherapy. Activated T cells directed against tumor-associated antigens are fully capable of recognizing and eradicating neoplastic cells. Therefore, HLA expression loss is considere

  5. Construction and Functional Test of HLA-A*2402-Peptide Tetramer

    Institute of Scientific and Technical Information of China (English)

    XiaolingLu; XiongwenWu; ZhihuiLiang; XiufangWeng; QingLi; FeiliGong

    2005-01-01

    HLA-A*2402 is one of the most frequent HLA-A allele in Asian population. To construct HLA-A*2402-peptide tetramers, the transmembrane and intracellular segments of HLA-A*2402 cDNA were replaced with BSP sequence to form a fusion gene of sHLA-A*2402-BSP. The sHLA-A*2402-BSP fusion protein and β2m were high-level expressed as insoluble aggregates in E.coli, and refolded to form an HLA-A*2402-peptide monomeric complex by dilution method in the presence of an antigenic peptide. The HLA-A*2402-peptide monomeric complex was biotinated and tetramized to prepare HLA-A*2402-peptide tetramer. Then using the HLA-A*2402-peptide tetramers to detect antigen-specific cytotoxic T lymphocyte (CTL) induced by artificial antigen presenting cell (aAPC) in vitro. The results showed that HLA-A*2402-peptide tetramer was prepared correctly, and functional in detecting antigen-specific CTL in vitro, HLA-A*2402-peptide monomeric and its multimeric complexes are expected to provide a powerful tool for studying mechanisms of immune-related diseases in Asian populations .Cellular & Molecular Immunology. 2005;2(2): 145-149.

  6. Development of a humanized HLA-A2.1/DP4 transgenic mouse model and the use of this model to map HLA-DP4-restricted epitopes of HBV envelope protein.

    Directory of Open Access Journals (Sweden)

    Zhitao Ru

    Full Text Available A new homozygous humanized transgenic mouse strain, HLA-A2.1(+/+HLA-DP4(+/+ hCD4(+/+mCD4(-/-IAβ(-/-β2m(-/- (HLA-A2/DP4, was obtained by crossing the previously characterized HLA-A2(+/+β2m(-/- (A2 mouse and our previously created HLA-DP4(+/+ hCD4(+/+mCD4(-/-IAβ(-/- (DP4 mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4 inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans.

  7. Polymorphism of exon 3 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Meldgaard, Michael; Sørensen, S;

    1997-01-01

    HLA-G is a non-classical MHC class I gene with a limited tissue distribution. The most pronounced expression is detected in the cytotrophoblast of first trimester placenta. It is possible to detect mRNA for HLA-G in preimplantation blastocysts where expression is correlated with a high cleavage...... rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...... populations have only revealed a limited polymorphism. We investigated the polymorphism of the exon 3 of HLA-G by means of Polymerase Chain Reaction (PCR)-Single Strand Conformation Polymorphism (SSCP)- and DNA sequencing analysis in a Danish population. We detected four single-base substitutions in exon 3...

  8. Association study between HLA-DRB, HLA-DQA1, HLA-DQB1 and breast cancer in Iranian women

    Directory of Open Access Journals (Sweden)

    Amirzargar AA

    2010-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Based on the reports, high frequency of special alleles of HLA class II genes might be associated with susceptibility to or protective from a particular cancer. These alleles might vary depending on the geographical region. Here we investigate the association between alleles of HLA class II genes and breast cancer in Iranian women."n"nMethods: 100 patients with pathologically proved breast cancer who referred to Cancer Institute, Tehran University of Medical Sciences in Tehran, Iran, were divided to two groups based on ages (40 years old and less/ or more than 40 years old and were randomly selected and compared with a group of 80 healthy blood donor subjects. HLA class II alleles were determined by amplification of DNA with polymerase chain reaction (PCR method followed by HLA-typing using sequence-specific primer (SSP for each allele."n"nResults: The most frequent alleles in the DR and DQ regions in group 1 (40 years old and less in comparison with control group were HLA-DQA1*0301 (p=0.002 and HLA-DQB1*0302 (p>0.05. In contrast HLA-DQA1*0505 (p=0.004 had significantly lower frequency in this group compared with control group. Patients of group two (more than 40 years old had a higher frequencies of HLA

  9. An extended HLA-D region haplotype associated with celiac disease.

    Science.gov (United States)

    Howell, M D; Smith, J R; Austin, R K; Kelleher, D; Nepom, G T; Volk, B; Kagnoff, M F

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. We previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II beta-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. We now report the isolation of this beta-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP beta chain. This celiac disease-associated HLA-DP beta-chain gene was flanked by HLA-DP alpha-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP alpha-chain genes of celiac disease patients also were studied by RFLP analysis; 84% of HLA-DR3, -DQw2 patients had a 16-kb Xba I fragment that was present in only 36% of HLA-DR3, -DQw2 controls. Moreover, 79% of these patients had both alpha- and beta-chain polymorphisms in contrast to 27% of controls. Thus, celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP alpha- and beta-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion. Images PMID:2893373

  10. New Developments in HLA-G in Cardiac Transplantation.

    Science.gov (United States)

    Lazarte, Julieta; Tumiati, Laura C; Rao, Vivek; Delgado, Diego H

    2016-09-01

    Human Leukocyte Antigen-G (HLA-G) is a non-classical class 1b protein, whose gene is located on chromosome 6 (6p21.31). HLA-G inhibits the immune cells' cytotoxic activity by interacting with specific receptors on their membranes. Since it is a naturally occurring immune modulator, HLA-G has been investigated in transplantation. Indeed, a number of investigations reveal that HLA-G expression is influenced by genetic polymorphisms and in turn, those polymorphisms are associated with detrimental or beneficial outcomes in various pathological situations. The present review introduces the HLA-G molecule, the gene and its polymorphisms. It focuses on the expression of HLA-G and the role of polymorphisms primarily in heart transplant outcomes, secondarily in other transplant organs, as well as the role of the allograft and effect of medical therapy. We discuss the limitations in HLA-G transplant investigations and future directions. The immune inhibiting activity of HLA-G has a great deal of potential for its utilization in enhancing diagnostic, preventive and therapeutic strategies against rejection in the setting of transplantation. PMID:26707934

  11. The probability of finding HLA identical or partially matched unrelated donors in the population of Vojvodina

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2006-01-01

    Full Text Available Introduction. Allogeneic bone marrow transplantation and hematopoietic stem cell transplantation from unrelated donors are treatments of choice for patients lacking HLA identical siblings or family matched donors. Material and methods. Class I HLA typing was performed by using a standard micro-lymphocytotoxicyty test in 434 unrelated persons from Vojvodina, while, class II HLA typing was performed using a modified immunofluorescent technique. The estimated gene frequencies for the populations of Crete, Korea, China, Scotland, Romania, and North America, were used to calculate phenotype frequencies, the probability of finding HLA identical or partially (in 5/6 HLA antigens matched unrelated donors, the number of donors necessary for research, as well as genetic distances between populations. Results. The probability of finding HLA identical or partially matched unrelated donors for patients from Vojvodina is higher in closely related populations with low genetic distances, such as populations of Crete, Romania and Scotland. Discussion. The probability of finding HLA identical or partially matched unrelated donors is in inverse proportion with the number of unrelated donors necessary for research with aim of finding at least one HLA compatible donor. Conclusion. The probability of finding compatible unrelated donors depends on the degree of HLA matching between the donor and recipient, HLA phenotype frequencies and the donor pool size. These methodology may have a wider usage, because it can be applied in calculating the probability of finding suitable genotypically matched donors, by using HLA allele frequencies defined by molecular techniques. .

  12. HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jakobsen, B K;

    1986-01-01

    We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR....../DQ. The suppression was analyzed with special reference to the sharing of HLA-antigens between (i) the stimulator in the MLR and (ii) the stimulator generating the PL. HLA-DP and HLA-DR/DQ antigens were equally capable of generating suppressor cells. When these cells were added to MLRs, the specific...... stimulators induced the strongest suppression (74%), while allogeic cells sharing class II antigens induced a slightly weaker suppression (66%). The suppression related to HLA-DP (60%) was almost identical to that related to HLA-DR/DQ (59%). The HLA-A, B, C related suppression was of the same magnitude (58...

  13. The role of HLA-B27 in inflammatory arthritis

    OpenAIRE

    Lynch, Sarah Janice

    2009-01-01

    Electronic version excludes material for which permission has not been granted by the rights holder The MHC class I allele, HLA-B27, is strongly associated with a group of inflammatory arthritic conditions collectively known as spondyloarthropathies (SpA). Ankylosing spondylitis (AS) shows the strongest association with 90-95 % of patients being HLA-B27 positive. The relationship between HLA-B27 and SpA has been known for over 30 years, however despite ongoing research, the reason for thi...

  14. Diversity of Extended HLA-DRB1 Haplotypes in the Finnish Population

    OpenAIRE

    Wennerström, Annika; Vlachopoulou, Efthymia; Lahtela, L. Elisa; Paakkanen, Riitta; Eronen, Katja T.; Seppänen, Mikko; Lokki, Marja-Liisa

    2013-01-01

    The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included ...

  15. Role for HLA in susceptibility to infectious mononucleosis

    OpenAIRE

    Farrell, Paul J

    2007-01-01

    Factors involved in determining whether infectious mononucleosis occurs after primary EBV infection may include age, dose of virus received, and various genetic markers. A study by McAulay and colleagues reported in this issue of the JCI shows that the presence of certain HLA class I alleles correlates with the incidence and severity of infectious mononucleosis (see the related article beginning on page 3042). These same HLA alleles are also risk factors for EBV-associated Hodgkin lymphoma (H...

  16. HLA-B*5701 testing to predict abacavir hypersensitivity

    OpenAIRE

    Ma, Joseph D.; Lee, Kelly C.; Kuo, Grace M

    2010-01-01

    Abacavir is a nucleoside reverse transcriptase inhibitor used for combination antiretroviral therapy for treating human immunodeficiency virus (HIV) infection. An adverse effect from abacavir is a treatment-limiting hypersensitivity reaction, which can be severe and potentially life-threatening. Abacavir-induced hypersensitivity reaction has been associated with the presence of the major histocompatibility complex class I allele HLA-B*5701. A screening test for the HLA-B*5701 allele can assis...

  17. The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch.

    Science.gov (United States)

    Celik, Alexander A; Kraemer, Thomas; Huyton, Trevor; Blasczyk, Rainer; Bade-Döding, Christina

    2016-01-01

    Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK cell-mediated killing. Low in polymorphisms, two alleles are widely expressed among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles present a limited set of peptides derived from class I leader sequences physiologically; however, HLA-E*01:01 presents non-canonical peptides in the absence of HLA class I molecules. To further assess the functional differences between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by applying soluble HLA technology followed by mass-spectrometric peptide sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids and differed in their biophysical properties, no overlap in the peptide repertoire of both allelic variants could be observed; however, both alleles shared marginal peptides from the same proteomic content. Artificial APCs expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized using cognate HLA class I-derived peptide ligands to analyze the impact of residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. Differences in peptide stabilization could be translated to the density and half-life time of peptide-HLA-E molecules on the cell surface that subsequently impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, these data illustrate functional differences of HLA-E allelic variants induced by a single amino acid. Furthermore, the function of HLA-E in pathophysiologic situations when the HLA processing machinery is interrupted seems to be more emphasized than previously described, implying a crucial role for HLA-E in tumor or viral immune episodes. PMID:26552660

  18. ENDOGENOUS EXPRESSION AND HLA STABILIZATION ASSAY OF PLASMODIUM FALCIPARUM CTL EPITOPE MINIGENE IN HUMAN HLA-A2.1 AND HLA-B51 CELLS

    Institute of Scientific and Technical Information of China (English)

    唐玉阳; 王恒

    2001-01-01

    Objective. To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. Methods. Synthesized oligonucleotides encoding for P.f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT-PCR and HLA stabilization assay. Results. Two mini-genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA-B51, SH6 which was restricted to HLA-A2.1, and TS, which had the two aforementioned mini-genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini-gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. Conclusion. A successful expression and presentation of multiple CTL epitope mini-gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope plasmodium falciparum DNA vaccine that could cover most of Chinese population.

  19. [HLA and keloids: antigenic frequency and therapeutic response].

    Science.gov (United States)

    Rossi, A; Bozzi, M

    1989-01-01

    Twenty keloid subjects were typed for class 1 (HLA-A, B and C) and class 2 (HLA-DR and DQ) histocompatibility antigens. Their frequencies were compared to those found in control populations. Of all the antigens belonging to class 1, B 21 was more prevalent in patients. The findings regarding class 2 antigens were noteworthy: in keloid patients there was a significant prevalence of DR 5 (RR = 3.54 and 7.93 respectively for the two control groups) and DQw 3 (RR = 16.8). The patients typed for HLA-antigens were treated with corticosteroid infiltrations. The responses to the treatments were no related to the histocompatibility antigens. PMID:2628278

  20. Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis

    OpenAIRE

    Tuokko, J; Reijonen, H.; Ilonen, J; K. Anttila; Nikkari, S; Mottonen, T; Yli-Kerttula, U; Toivanen, A

    1997-01-01

    OBJECTIVE—To study HLA class II association in reactive arthritis.
METHODS—63 patients with reactive arth-ritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing.
RESULTS—46 (73%) of 63 patients with reactive arthr...

  1. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

    Directory of Open Access Journals (Sweden)

    Antony N. Antoniou

    2011-01-01

    Full Text Available The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs which include ankylosing spondylitis (AS and Reactive Arthritis (ReA, has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with the SpAs. Recent investigations have focused on the unusual biochemical structures of HLA-B27 and their potential role in SpA pathogenesis. Here we discuss how these unusual biochemical structures may participate in cellular events leading to chronic inflammation and thus disease progression.

  2. HLA in bone marrow transplantation

    International Nuclear Information System (INIS)

    It has been well understood that human major histocompatibility antigen system, HLA is the most important role in the allo transplantation. Therefore, the structure of HLA genes was presented by the recent information (1987). Moreover, their functions in vitro and in vivo also were described. Finally, bone marrow transplantation and HLA network system in Japan against HLA mismatched case was proposed. It is eagerly expected that functional and clinical bone marrow transplantation in Japan could be succeeded. (author)

  3. Complete sequence of HLA-B27 cDNA identified through the characterization of structural markers unique to the HLA-A, -B, and -C allelic series

    Energy Technology Data Exchange (ETDEWEB)

    Szoets, H.; Reithmueller, G.; Weiss, E.; Meo, T.

    1986-03-01

    Antigen HLA-B27 is a high-risk genetic factor with respect to a group of rheumatoid disorders, especially ankylosing spondylitis. A cDNA library was constructed from an autozygous B-cell line expressing HLA-B27, HLA-Cw1, and the previously cloned HLA-A2 antigen. Clones detected with an HLA probe were isolated and sorted into homology groups by differential hybridization and restriction maps. Nucleotide sequencing allowed the unambiguous assignment of cDNAs to HLA-A, -B, and -C loci. The HLA-B27 mRNA has the structure features and the codon variability typical of an HLA class I transcript but it specifies two uncommon amino acid replacements: a cysteine in position 67 and a serine in position 131. The latter substitution may have functional consequences, because it occurs in a conserved region and at a position invariably occupied by a species-specific arginine in humans and lysine in mice. The availability of the complete sequence of HLA-B27 and of the partial sequence of HLA-Cw1 allows the recognition of locus-specific sequence markers, particularly, but not exclusively, in the transmembrane and cytoplasmic domains.

  4. Impact of HLA-G analysis in prevention, diagnosis and treatment of pathological conditions

    Science.gov (United States)

    Bortolotti, Daria; Gentili, Valentina; Rotola, Antonella; Cassai, Enzo; Rizzo, Roberta; Luca, Dario Di

    2014-01-01

    Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule that differs from classical HLA class I molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-modulatory and anti-inflammatory function on both innate and adaptative immunity. This peculiar characteristic of HLA-G has led to investigations of its role in pathological conditions in order to define possible uses in diagnosis, prevention and treatment. In recent years, HLA-G has been shown to have an important implication in different inflammatory and autoimmune diseases, pregnancy complications, tumor development and aggressiveness, and susceptibility to viral infections. In fact, HLA-G molecules have been reported to alternate at both genetic and protein level in different disease situations, supporting its crucial role in pathological conditions. Specific pathologies show altered levels of soluble (s)HLA-G and different HLA-G gene polymorphisms seem to correlate with disease. This review aims to update scientific knowledge on the contribution of HLA-G in managing pathological conditions. PMID:25237627

  5. Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells

    OpenAIRE

    Santos, Susana G.; Lynch, Sarah; Campbell, Elaine C.; Antoniou, Antony N.; Simon J Powis

    2008-01-01

    Introduction Ankylosing spondylitis (AS) is a severe, chronic inflammatory arthritis, with a strong association to the human major histocompatibilty complex (MHC) class I allele human leucocyte antigen (HLA) B27. Disulfide-linked HLA-B27 heavy-chain homodimers have been implicated as novel structures involved in the aetiology of AS. We have studied the formation of HLA-B27 heavy-chain homodimers in human dendritic cells, which are key antigen-presenting cells and regulators of mammalian immun...

  6. Immune response to immunodominant Mycobacterium tuberculosis antigen ESAT-6 derived peptide is HLA-haplotype dependent

    OpenAIRE

    Smart, Michele; Behrens, Marshall; David, Luckey; Conway, Catherine; Taneja, Veena

    2014-01-01

    The antigenic proteins of Mycobacterium tuberculosis (Mtb) have been defined. We used synthetic peptides of secreted antigens, early secreted antigenic target 6 (ESAT-6) and cultural filtrate protein-10 (CFP-10), of Mtb and characterized the immune response in context of HLA genes. Humanized mice lacking endogenous class II molecules but expressing various human DR and DQ HLA transgenes singly or as a haplotype were used to study the HLA-mediated immune response to peptides. Our observations ...

  7. HLA-B27: natural function and pathogenic role in spondyloarthritis

    OpenAIRE

    McMichael, Andrew; Bowness, Paul

    2002-01-01

    Chapter summary The human leukocyte antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides collectively known as the spondyloarthritides. We have set out to define the natural immunological function of HLA-B27, and then to apply this knowledge to understand its pathogenic role. Human leukocyte antigen class 1 molecules bind antigenic peptides for cell surface presentation to cytotoxic T lymphocytes. HLA-B27 binds and presents peptides from influenza, HI...

  8. HLA-A29-Positive Uveitis: Birdshot Chorioretinopathy, What Else

    Directory of Open Access Journals (Sweden)

    Ilaria Zucchiatti

    2013-12-01

    Full Text Available Birdshot chorioretinopathy (BSCR is a relatively rare form of uveitis, which is strongly correlated with the histocompatibility leukocyte antigen (HLA-A29 class I type. Nevertheless, HLA typing is not diagnostic. The purpose of the present study was to retrospectively evaluate the ocular manifestations associated with the presence of HLA-A29 other than typical BSCR. Charts of consecutive patients with a diagnosis of intraocular inflammation and who were found to be positive for the presence of HLA-A29 were retrospectively reviewed. Only 7 patients met the criteria for a definite diagnosis of BSCR. Among the other 11 patients, the disease was bilateral in 7 patients and unilateral in 4 patients. A definite diagnosis of the following conditions were found: intraocular and CNS lymphoma in 1 patient, posterior tubercular uveitis with occlusive vasculitis in 1 patient, latent ocular tuberculosis in 1 patient, Fuchs' uveitis in 1 patient, herpetic panuveitis in 1 patient and HLA-B27 anterior uveitis in another patient. Although BSCR is strongly related to the HLA-A29 phenotype, and its presence confers a relative risk of disease, the definite diagnosis requires specific ocular characteristics. HLA-A29 typing alone is not a diagnostic requirement for the definite diagnosis of BSCR and should only be considered as a supportive finding.

  9. Distribution of HLA antigens in families of patients with leukaemias

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2008-01-01

    Full Text Available Introduction. Since the discovery of major histocompatihility complex influence on manse leukaemia in 1964, an HLA association with leukaemia in humans has been considered as a possible genetic risk factor that contributes to development of leukaemia. In addition to associations of several IILA antigens with leukaemias, it has been observed that patients with leukaemia have an increase in the frequency of HLA identical siblings, higher degree of HLA compatibility with their parents as well as higher parental HLA sharing rate in comparison to the families without patients suffering from leukaemia. Material and methods. To test hypothesis that susceptibility to leukaemia can be caused bv influence of a recessive genes associated with the major histocompatibilily complex in man, we analyzed the distribution of I class HLA antigens in 77 families of patients suffering from different types of leukaemia. In the affected families and in 72 families of healthy controls, we investigated HLA identical sibling frequency, parental sharing of one, two or three HLA antigens and degree of compatibility of parents and off springs: existence of haploidentity, compatibility in l' and 4/4 HLA antigens of A and B loci. Results We have found that in families with affected persons there is a statistically significant difference in number of HLA identical siblings in comparison to the group of healthy controls (t=2,63. Also the results have shown that among the parents of affected persons there is a statistically significant difference in mutual compatibility in one (t=3,012 and two ft= 2,4 HLA antigens. In addition, we observed an increase in the frequency of higher rate of compatibility between patients and their parents (t=3,88 in l' HLA antigens, to their mothers (t=2,83 and to their fathers (t=2,55, respectively, in comparison to the healthy control group. Conclusion The results of this study show that in families with persons suffering from leukaemia there are

  10. Presence of HLA-DR molecules and HLA-DRB1 mRNA in circulating CD4+ T cells

    DEFF Research Database (Denmark)

    Revenfeld, Anne Louise Schacht; Steffensen, Rudi; Pugholm, Lotte Hatting;

    2016-01-01

    The human major histocompatibility complex class II (MHCII) isotype HLA-DR is currently used as an activation marker for T cells. However, whether an endogenous protein expression or a molecular acquisition accounts for the presence of HLA-DR on T cells remains undetermined and still controversial....... In order to further characterize this phenomenon, we compared several aspects of the presence of the HLA-DR protein to the presence of associated mRNA (HLA-DRB1), focusing on human T cells from peripheral blood of healthy individuals. Using a flow cytometric approach, we determined that the HLA......-DR observed on CD4+ T cells was almost exclusively cell surface-associated, while for autologous CD19+ B cells, the protein could be located in the plasma membrane as well as in the cytoplasm. Moreover, negligible expression levels of HLA-DRB1 were found in CD4+ T cells, using an HLA-DRB1 allele-specific q...

  11. Maternal homozygocity for a 14 basepair insertion in exon 8 of the HLA-G gene and carriage of HLA class II alleles restricting HY immunity predispose to unexplained secondary recurrent miscarriage and low birth weight in children born to these patients

    DEFF Research Database (Denmark)

    Christiansen, Ole B; Kolte, Astrid Marie; Dahl, Mette;

    2012-01-01

    Homozygous carriage of a 14 base pair (bp) insertion in exon 8 of the HLA-G gene may be associated with low levels of soluble HLA-G and recurrent miscarriage (RM). We investigated the G14bp insertion(ins)/deletion(del) polymorphism in 339 women with unexplained RM and 125 control women. In all...... patients and patients with secondary RM after a firstborn boy, 19.2% and 23.9%, respectively, were G14bp ins/ins compared with 11.2% of controls (p...

  12. DECREASED FREQUENCY OF HLA-DR13DR6 IN WEGENERS GRANULOMATOSIS

    NARCIS (Netherlands)

    HAGEN, EC; STEGEMAN, CA; DAMARO, J; SCHREUDER, GMT; LEMS, SPM; TERVAERT, JWC; DEJONG, GM; HENE, RJ; KALLENBERG, CGM; DAHA, MR; VANDERWOUDE, FJ

    1995-01-01

    The pathogenesis of Wegener's granulomatosis, microscopic polyangiitis and idiopathic rapidly progressive glomerulonephritis (RPGN) is still unclear; in vitro data support both humoral and cellular autoimmune mechanisms. An association of Wegener's granulomatosis with HLA antigens has been described

  13. Distribution of HLA-A, -B, and -C Alleles and HLA/KIR Combinations in Han Population in China

    Directory of Open Access Journals (Sweden)

    Yunsong Shen

    2014-01-01

    Full Text Available We investigated polymorphisms of the human leukocyte antigen (HLA class I (A, B, and C loci of a Han population (n, 239 from the Yunnan province, Southwest China, using high-resolution polymerase chain reaction-Luminex (PCR-Luminex typing. We combined the HLA data from this study with the KIR genotypes from a previous study of this Han population to analyze the combination of KIR/HLA ligands. A total of 27 HLA-A, 54 HLA-B, and 31 HLA-C alleles were found in this population. The frequencies of A*11:01, A*24:02, B*40:01, B*46:01, C*01:02, C*03:04, and C*07:02 were all > 10%. The following haplotypes were common, with frequencies > 5%: 1 A-B (A*02:07-B*46:01, 2 A-C (A*02:07-C*01:02, and A*11:01-C*07:02, 4 C-B (B*13:01-C*03:04, B*40:01-C*07:02, B*46:01-C*01:02 and B*58:01-C*03:02, and 1 A-C-B (A*02:07-C*01:02-B*46:01. Analysis of KIR3D and their ligands HLA-A3/A11 and HLA-Bw4 showed that the frequencies of 3DL2+-A3/A11+ and 3DL2+-A3/A11− were 0.527 and 0.473, and the frequencies of 3DL1+-Bw4+, 3DL1+-Bw4−, 3DL1−-Bw4+, and 3DL1−-Bw4− were 0.552, 0.397, 0.038, and 0.013, respectively. The results of KIR/HLA-C combination analysis showed that all individuals had at least one inhibitory or activating KIR/HLA-C pair, and one KIR/HLA-C pair was the most frequent (157/239, followed by two pairs (46/239, three pairs (33/239, and no pairs (3/239. Comparison of KIR gene and HLA gene and their pair frequency between Yunnan Han and the isolated Han (FYDH who also lived in Yunnan province showed no significant difference (P>0.05 in KIR frequencies, but significant differences (P0.05 between the two populations for KIR/HLA pairs.

  14. Molecular basis for HLA-DQ associations with IDDM.

    Science.gov (United States)

    Nepom, G T; Kwok, W W

    1998-08-01

    Autoimmune diabetes is the clinical end point for a sequential cascade of immunologic events that occur in a genetically susceptible individual. Structural and functional analysis of the HLA class II susceptibility genes in IDDM suggests likely molecular mechanisms for several of the key steps in this cascade of autoimmune events. We outline a pathway in which the HLA-DQ genes associated with IDDM bias the immunologic repertoire toward autoimmune specificities, creating an autoimmune-prone individual, followed by amplification and triggering events that promote subsequent immune activation. There are several direct links between genetics and autoimmune disease in this pathway: the developmental maturation of T-cells in a genetically susceptible individual occurs through molecular interactions between the T-cell receptor and the HLA-peptide complex. Selection of T-cells with receptors likely to contribute to autoreactivity may preferentially occur in the context of specific HLA-DQ alleles that are diabetes prone, because of inefficiencies in the peptide-MHC structural interactions of these molecules. Subsequent activation of these T-cells in the context of recognizing islet-associated antigens can trigger a poorly regulated immune response that results in progressive islet destruction. These subsequent diabetes-specific events are also directed by specific HLA genes, most prominently by the binding of specific antigenic peptides by the disease-associated HLA molecules. In this sequential cascade, opportunities for environmental influences and modulation by non-HLA genes are identified that likely act in concert with the predominant genetic susceptibility contributed by the HLA molecules themselves. Clarification of the steps in this pathway extends our understanding of the prevailing role of HLA genes in IDDM pathogenesis and suggests opportunities to intervene at discrete initiating, disease-promoting, or regulatory steps in IDDM development. PMID:9703314

  15. Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies

    OpenAIRE

    1995-01-01

    Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called "spondyloarthropathies." Studies on transgenic rats expressing HLA-B27 and human beta 2-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin (B27+ beta 2m-/- ). In the absence of beta 2-microglobulin, B27+ beta 2m-/- animals do not express the HLA-B27 tran...

  16. Identification of three novel human leukocyte antigen alleles, HLA-B*58:43, HLA-C*03:190, and HLA-DPA1*01:12, in an East African cohort.

    Science.gov (United States)

    Nykoluk, M; Bailey, R C; Moses, S; Plummer, F A; Luo, M

    2013-08-01

    Three novel human leukocyte antigen (HLA) alleles were identified using a sequence-based typing of HLA class I and class II alleles of 1867 participants from a male circumcision cohort in Kenya. The new alleles were first identified by sequencing and then confirmed by cloning the polymerase chain reaction (PCR) products and sequencing multiple clones. HLA-B*58:43 was identical to HLA-B*58:02 with the exception of a nucleotide change at codon 125 in exon 3 (GCC→ACC), and resulted in the amino acid change from Alanine to Threonine. HLA-C*03:190 was identical to HLA-C*03:02:01 with the exception of a nucleotide change at codon 131 in exon 3 (CGC→TGC), and resulted in the amino acid change from Arginine to Cysteine. HLA-DPA1*01:12 was identical to HLA-DPA1*01:03:01:01 with the exception of a nucleotide change at codon 66 in exon 2 (TTG→TCG), and resulted in the amino acid change from Leucine to Serine. PMID:23849069

  17. MiRNA-mediated control of HLA-G expression and function.

    Directory of Open Access Journals (Sweden)

    Irit Manaster

    Full Text Available HLA-G is a non-classical HLA class-Ib molecule expressed mainly by the extravillous cytotrophoblasts (EVT of the placenta. The expression of HLA-G on these fetal cells protects the EVT cells from immune rejection and is therefore important for a healthy pregnancy. The mechanisms controlling HLA-G expression are largely unknown. Here we demonstrate that miR-148a and miR-152 down-regulate HLA-G expression by binding its 3'UTR and that this down-regulation of HLA-G affects LILRB1 recognition and consequently, abolishes the LILRB1-mediated inhibition of NK cell killing. We further demonstrate that the C/G polymorphism at position +3142 of HLA-G 3'UTR has no effect on the miRNA targeting of HLA-G. We show that in the placenta both miR-148a and miR-152 miRNAs are expressed at relatively low levels, compared to other healthy tissues, and that the mRNA levels of HLA-G are particularly high and we therefore suggest that this might enable the tissue specific expression of HLA-G.

  18. Disulfide bond-mediated dimerization of HLA-G on the cell surface.

    Science.gov (United States)

    Boyson, Jonathan E; Erskine, Robert; Whitman, Mary C; Chiu, Michael; Lau, Julie M; Koopman, Louise A; Valter, Markus M; Angelisova, Pavla; Horejsi, Vaclav; Strominger, Jack L

    2002-12-10

    HLA-G is a nonclassical class I MHC molecule with an unknown function and with unusual characteristics that distinguish it from other class I MHC molecules. Here, we demonstrate that HLA-G forms disulfide-linked dimers that are present on the cell surface. Immunoprecipitation of HLA-G from surface biotinylated transfectants using the anti-beta2-microglobulin mAb BBM.1 revealed the presence of an approximately equal 78-kDa form of HLA-G heavy chain that was reduced by using DTT to a 39-kDa form. Mutation of Cys-42 to a serine completely abrogated dimerization of HLA-G, suggesting that the disulfide linkage formed exclusively through this residue. A possible interaction between the HLA-G monomer or dimer and the KIR2DL4 receptor was also investigated, but no interaction between these molecules could be detected through several approaches. The cell-surface expression of dimerized HLA-G molecules may have implications for HLA-Greceptor interactions and for the search for specific receptors that bind HLA-G. PMID:12454284

  19. Evaluation of a competitive enzyme-linked immunosorbent assay for measurements of soluble HLA-G protein

    DEFF Research Database (Denmark)

    Rasmussen, M; Dahl, M; Buus, S;

    2014-01-01

    The human leukocyte antigen (HLA) class Ib molecule, HLA-G, has gained increased attention because of its assumed important role in immune regulation. The HLA-G protein exists in several soluble isoforms. Most important are the actively secreted HLA-G5 full-length isoform generated by alternative...... splicing retaining intron 4 with a premature stop codon, and the cleavage of full-length membrane-bound HLA-G1 from the cell surface, so-called soluble HLA-G1 (sHLA-G1). A specific and sensitive immunoassay for measurements of soluble HLA-G is mandatory for conceivable routine testing and research projects....... We report a novel method, a competitive immunoassay, for measuring HLA-G5/sHLA-G1 in biological fluids. The sHLA-G immunoassay is based upon a competitive enzyme-linked immunosorbent assay (ELISA) principle. It includes a recombinant sHLA-G1 protein in complex with β2-microglobulin and a peptide as a...

  20. Residues Met76 and Gln79 in HLA-G α1 domain involved in KIR2DL4 recognition

    Institute of Scientific and Technical Information of China (English)

    Wei Hua YAN; Li An FAN

    2005-01-01

    Human leukocyte antigen-G (HLA-G) has long been speculated as a beneficial factor for a successful pregnancy for its restricted expression on fetal-maternal extravillous cytotrophoblasts and its capability of modulating uterine natural killer cell (uNK) function such as cytotoxicity and cytokine production through NK cell receptors. HLA class I α1domain is an important killer cell Ig-like receptor (KIR) recognition site and the Met76 and Gln79 are unique to HLA-G in this region. NK cell receptor KIR2DL4 is a specific receptor for HLA-G, yet the recognition site on HLA-G remains unknown. In this study, retroviral transduction was applied to express the wild type HLA-G (HLA-wtG), mutant HLA-G (HLA-mG) on the chronic myelogenous leukemia cell line K562 cells and KIR2DL4 molecule on NK-92 cells,respectively. KIR2DL4-IgG Fc fusion protein was generated to determine the binding specificity between KIR2DL4and HLA-G. Our results showed that residue Met76, Gln79 mutated to Ala76,79 in the α1 domain of HLA-G protein could affect the binding affinity between KIR2DL4 and HLA-G, meanwhile, the KIR2DL4 transfected NK-92 cells (NK-92-2DL4) showed a considerably different cytolysis ability against the HLA-wtG and HLA-mG transfected K562 targets.Taken together, our data indicated that residue Met76 and Gln79 in HLA-G α1 domain plays a critical role in the recognition of KIR2DL4, which could be an explanation for the isoforms of HLA-G, all containing the α1 domain, with the potential to regulate NK functions.

  1. HLA polymorphism in Sudanese renal donors

    Directory of Open Access Journals (Sweden)

    Ameer M Dafalla

    2011-01-01

    Full Text Available The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA antigens and haplotype frequencies (HFs in the study subjects. HLA typing was performed using the complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals selected as donors in the Sudanese Renal Transplantation Program. Considerable polymorphism was observed at each locus; A2 (0.28, A30 (0.12, A3 (0.09, A24 (0.09, A1 (0.09, and A68 (0.06 were the most frequent antigens in the A locus, while B51 (0.092, B41 (0.081, B39 (0.078, B57 (0.060, B35 (0.068, B 50 (0.053 and B 52 (0.051 were the most common B locus antigens. DR13 (0.444 and DR15 (0.160 showed the highest antigen frequencies (AFs in the DR locus. In the DQ locus, DQ1 showed the highest gene frequency (0.498, while DQ2 and DQ3 AFs were (0.185 and (0.238, respectively. The most common HLA-A and -B haplotypes in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe-stocks of the study subjects (Gaalia, Nile Nubian and Johyna were A24, B38 for Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian. These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

  2. Sibling rivalry: competition between MHC class II family members inhibits immunity.

    Science.gov (United States)

    Denzin, Lisa K; Cresswell, Peter

    2013-01-01

    Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation. PMID:23288359

  3. The Mycobacterium tuberculosis phagosome is a HLA-I processing competent organelle.

    Directory of Open Access Journals (Sweden)

    Jeff E Grotzke

    2009-04-01

    Full Text Available Mycobacterium tuberculosis (Mtb resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+ T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib. Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens.

  4. Diversity of extended HLA-DRB1 haplotypes in the Finnish population.

    Directory of Open Access Journals (Sweden)

    Annika Wennerström

    Full Text Available The Major Histocompatibility Complex (MHC, 6p21 codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1. The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism. The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A*03∼B*35∼DRB1*01∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A*01∼B*08∼DRB1*03∶01. Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population

  5. Polymorphism of HLA-A and HLA-B in pre-eclampsia%HLA-A和HLA-B的多态性与先兆子痫

    Institute of Scientific and Technical Information of China (English)

    张展; 贾莉婷; 张琳琳

    2009-01-01

    Objective: To investigate the association between the polymorphism of HLA-A, HLA-B genes and pre-eclampsia. Methods: HLA-A, HLA-B genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) in 119 preeclampsia patients, 117 normal pregnant women and their neonates. Results: The study showed that 16 HLA-A and 39 HLA-B alleles were obtained in pre-eclamptic patients and normal pregnant women. 15 HLA-A and 37 HLA-B alleles were obtained in their neonates. No significant difference was found in maternal or neonatal HLA-A, HLA-B alleles be-tween pre-eclampsia group and control group (Pc>0. 05). The frequencies of HLA-A11, HLA-A24,HLA-B13, HLA-B14, HLA-B15, HLA-B52 maternal/fetus genetic assoications were significantly different between pre-eclampsia group and control group (P<0. 05). Conclusion: Some HLA-A, HLA-B maternal/fetus special bindings may be associated with the susceptibility or protective of pre-eclampsia.

  6. Co-dominant expression of the HLA-G gene and various forms of alternatively spliced HLA-G mRNA in human first trimester trophoblast

    DEFF Research Database (Denmark)

    Hviid, T V; Møller, C; Sørensen, S;

    1998-01-01

    -implantation developmental processes. Animal studies of genomic imprinting of major histocompatibility complex (MHC) antigens in the placenta have shown discordant results. To address this issue in the human placenta, we examined the expression of the non-classical human leukocyte antigen (HLA) class I gene, HLA-G. Genomic...... imprinting of the HLA-G locus could have implications for the interaction in the feto-maternal relationship. Restriction Fragment Length Polymorphism (RFLP), allele-specific amplification and Single Strand Conformation Polymorphism (SSCP) analysis followed by DNA sequencing were performed on Reverse...... Transcription (RT) Polymerase Chain Reaction (PCR) products of HLA-G mRNA to examine the expression of maternal and paternal alleles. Our results demonstrate that HLA-G is co-dominantly expressed in first trimester trophoblast cells. A "new" non-synonymous base substitution in exon 4 was detected. We also...

  7. IDENTIFIKASI TIPE HLA KELAS II DENGAN TEKNIK PCR

    Directory of Open Access Journals (Sweden)

    Ervi Salwati

    2012-09-01

    Full Text Available HLA (Human Leukocyte Antigen contains a set of genes located together on the short arm of chromosome 6. These genes control immune responses, graft acceptance or rejection and tumor surveillance. These abilities have close relationship with genetic variation (occur in "many forms" or alleles that bind and present antigens to T lymphocytes. Using advanced technology and molecular biology approaches (PCR technique detection of genetic variation in the HLA region (or HLA typing has been performed based on DNA.. PCR is an in vitro technique to amplify the DNA sequence enzymatically. "Sequence Specific Primers" (SSP are designed for this PCR to obtain amplification of specific alleles or groups of alleles. The PCR products are visualized through agarose gel electrophoresis stained with ethidium bromide. The PCR technique requires small amount of whole blood (0.5 - 1 ml, gives rapid, accurate and complete result. This paper discuss identification of HLA class II typing using PCR-SSP technique and show the examples of the results.   Key words: HLA (Human Leukocyte Antigen class II, PCR (Polymerase Chain Reaction

  8. Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors

    DEFF Research Database (Denmark)

    Isa, Adiba; Nehlin, Jan; Sabir, Hardee Jawad;

    2010-01-01

    HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C...... at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either...... undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced...

  9. HLA-DP and bonemarrow transplantation: DP-incompatibility and severe acute graft versus host disease

    DEFF Research Database (Denmark)

    Ødum, Niels; Platz, P; Jakobsen, B K;

    1987-01-01

    The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15...... the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA...

  10. Receiver Operating Characteristic Analysis of HLA, CTLA4, and Insulin Genotypes for Type 1 Diabetes

    OpenAIRE

    Valdes, Ana M; Varney, Michael D.; Erlich, Henry A.; Noble, Janelle A

    2013-01-01

    OBJECTIVE This study assessed the ability to distinguish between type 1 diabetes–affected individuals and their unaffected relatives using HLA and single nucleotide polymorphism (SNP) genotypes. RESEARCH DESIGN AND METHODS Eight models, ranging from only the high-risk DR3/DR4 genotype to all significantly associated HLA genotypes and two SNPs mapping to the cytotoxic T-cell–associated antigen-4 gene (CTLA4) and insulin (INS) genes, were fitted to high-resolution class I and class II HLA genot...

  11. HLA-B27 antigen

    Science.gov (United States)

    ... colitis Psoriatic arthritis (arthritis associated with psoriasis) Reactive arthritis Sacroiliitis (inflammation of the sacroiliac joint) Uveitis If there are symptoms or signs of an autoimmune disease, a positive HLA-B27 test may confirm the diagnosis. However, HLA-B27 ...

  12. HLA-G expression levels influence the tolerogenic activity of human DC-10.

    Science.gov (United States)

    Amodio, Giada; Comi, Michela; Tomasoni, Daniela; Gianolini, Monica Emma; Rizzo, Roberta; LeMaoult, Joël; Roncarolo, Maria-Grazia; Gregori, Silvia

    2015-04-01

    Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified a subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations in the 3' untranslated region of the HLA-G locus of in vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G expression on DC-10 is donor-dependent. Functional studies demonstrated that DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote allo-specific anergic T cells that contain a significantly higher frequency of Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b(+)LAG-3(+) (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G expression on DC-10 is genetically imprinted, being associated with specific variations in the 3' untranslated region of the gene, and it may be finely tuned by microRNA-mediated post-transcriptional regulation. These data highlight the important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 cells at high frequency. These new insights into the role of HLA-G in DC-10-mediated induction of Tr1 cells provide additional information for clinical use in Tr1- or DC-10-based cell therapy approaches. PMID:25661445

  13. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    G. Caocci

    2016-04-01

    Full Text Available Non-classical human leucocyte antigen (HLA-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL, in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp deletion-insertion (del-ins polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy patients with a 2-year progression-free survival rate (PFS of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.

  14. HLA-B27, but not HLA-B7, immunodominance to influenza is ERAP dependent.

    Science.gov (United States)

    Akram, Ali; Lin, Aifeng; Gracey, Eric; Streutker, Catherine J; Inman, Robert D

    2014-06-15

    Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1) plays a critical role in the processing of peptides prior to binding to MHC class I molecules. In this article, we show for the first time, to our knowledge, that the HLA-B27 immunodominant influenza nucleoprotein (NP) 383-391 epitope is made as an N-terminally extended 14-mer before it is trimmed by ERAP. In the absence of ERAP, there is a significant reduction in the CTL response to the B27/NP383-391 epitope in influenza A (flu)-infected B27/ERAP(-/-) mice. With the use of tetramer staining, the number of naive CD8(+) T cells expressing TCR Vβ8.1 in B27/ERAP(-/-) transgenic mice is significantly lower than that seen in B27/ERAP(+/+) mice. HLA-B27 surface expression in naive and flu-infected B27/ERAP(-/-) mice is also lower than the expression seen for the same allele in naive and flu-infected B27/ERAP(+/+) mice. In contrast, surface expression of HLA-B7 was unaffected by the absence of ERAP in B7/ERAP(-/-) transgenic mice. The B7-restricted NP418-426 CTL response in flu-infected B7/ERAP(-/-) and B7/ERAP(+/+) mice was also similar. These results provide, to our knowledge, the first in vivo demonstration of ERAP functionally influencing host immune response in an HLA allele-specific manner. This principle has relevance to diseases such as ankylosing spondylitis, in which HLA-B27 and ERAP jointly contribute to disease predisposition. PMID:24835397

  15. Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis.

    Science.gov (United States)

    Saruhan-Direskeneli, Güher; Hughes, Travis; Yilmaz, Vuslat; Durmus, Hacer; Adler, Adam; Alahgholi-Hajibehzad, Mahdi; Aysal, Fikret; Yentür, Sibel P; Akalin, Mehmet Ali; Dogan, Oner; Marx, Alexander; Gülsen-Parman, Yesim; Oflazer, Piraye; Deymeer, Feza; Sawalha, Amr H

    2016-05-01

    This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey. PMID:27181991

  16. Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, Róisín M. [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Friis, Lone [University of Oxford, Oxford OX3 9DS (United Kingdom); Siebold, Christian [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Friese, Manuel A. [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Oxford OX3 9DU (United Kingdom); Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg (Germany); Fugger, Lars, E-mail: lars.fugger@imm.ox.ac.uk [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Oxford OX3 9DU (United Kingdom); Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej 100, 8200 N Aarhus (Denmark); Jones, E. Yvonne, E-mail: lars.fugger@imm.ox.ac.uk [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); University of Oxford, Oxford OX3 9DS (United Kingdom)

    2011-05-01

    The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of proteolipid protein, a myelin protein and candidate target for immune-mediated myelin destruction in MS. Comparison of the structure of HLA-A3 with that of HLA-A2, an MHC class I molecule which is protective against MS, indicates that both MHC class I molecules present very similar faces for T-cell receptor recognition whilst differing in the specificity of their peptide-binding grooves. These characteristics may underlie the opposing (predisposing versus protective) associations that they exhibit both in humans and in mouse models of MS-like disease. Furthermore, subtle alterations within the peptide-binding groove of HLA-A3 and other A3-like MHC class I molecules, members of the so-called A3 superfamily, may be sufficient to alter their presentation of autoantigen peptides such as KLIETYFSK. This in turn may modulate their contribution to the associated risk of autoimmune disease.

  17. Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy

    NARCIS (Netherlands)

    Geneugelijk, K; Hönger, G; van Deutekom, H W M; Thus, K A; Kesmir, C.; Hösli, I; Schaub, S; Spierings, E

    2015-01-01

    Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes pres

  18. Predicted indirectly recognizable HLA epitopes presented by HLA-DRB1 are related to HLA antibody formation during pregnancy

    NARCIS (Netherlands)

    Geneugelijk, K.; Hönger, G.; Van Deutekom, H. W M; Thus, K. A.; Keşmir, C.; Hösli, I.; Schaub, S.; Spierings, E.

    2015-01-01

    Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes pres

  19. Negative relationships between cellular immune response, Mhc class II heterozygosity and secondary sexual trait in the montane water vole

    Czech Academy of Sciences Publication Activity Database

    Charbonnel, N.; Bryja, Josef; Galan, M.; Deter, J.; Tollenaere, C.; Chaval, Y.; Morand, S.; Cosson, J.-F.

    2010-01-01

    Roč. 3, č. 3 (2010), s. 279-290. ISSN 1752-4571 Grant ostatní: 6th Framework Programme(XE) GOCE-2003-010284 EDEN Institutional research plan: CEZ:AV0Z60930519 Keywords : abundance cycles * Dqa and Drb * immunocompetence handicap * Mhc class II genes * parasite-mediated balancing selection * sexual selection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.145, year: 2010

  20. Definition of supertypes for HLA molecules using clustering of specificity matrices.

    Science.gov (United States)

    Lund, Ole; Nielsen, Morten; Kesmir, Can; Petersen, Anders Gorm; Lundegaard, Claus; Worning, Peder; Sylvester-Hvid, Christina; Lamberth, Kasper; Røder, Gustav; Justesen, Sune; Buus, Søren; Brunak, Søren

    2004-03-01

    Major histocompatibility complex (MHC) proteins are encoded by extremely polymorphic genes and play a crucial role in immunity. However, not all genetically different MHC molecules are functionally different. Sette and Sidney (1999) have defined nine HLA class I supertypes and showed that with only nine main functional binding specificities it is possible to cover the binding properties of almost all known HLA class I molecules. Here we present a comprehensive study of the functional relationship between all HLA molecules with known specificities in a uniform and automated way. We have developed a novel method for clustering sequence motifs. We construct hidden Markov models for HLA class I molecules using a Gibbs sampling procedure and use the similarities among these to define clusters of specificities. These clusters are extensions of the previously suggested ones. We suggest splitting some of the alleles in the A1 supertype into a new A26 supertype, and some of the alleles in the B27 supertype into a new B39 supertype. Furthermore the B8 alleles may define their own supertype. We also use the published specificities for a number of HLA-DR types to define clusters with similar specificities. We report that the previously observed specificities of these class II molecules can be clustered into nine classes, which only partly correspond to the serological classification. We show that classification of HLA molecules may be done in a uniform and automated way. The definition of clusters allows for selection of representative HLA molecules that can cover the HLA specificity space better. This makes it possible to target most of the known HLA alleles with known specificities using only a few peptides, and may be used in construction of vaccines. Supplementary material is available at http://www.cbs.dtu.dk/researchgroups/immunology/supertypes.html. PMID:14963618

  1. Detection of MAGE-A3Antigen and HLA-class I Gene Distribution in Lung Cancer%肺癌患者MAGE-A3抗原表达及HLA-I类基因分布的初步研究

    Institute of Scientific and Technical Information of China (English)

    庄东刚; 吴逸明; 巴月

    2004-01-01

    目的检测MAGE-A3抗原在肺癌组织中的表达情况以及HLA-I类基因在肺癌患者中的分布水平,以预测能够应用以MAGE-A3抗原蛋白为基础的肿瘤疫苗进行肿瘤免疫治疗的肺癌患者的比例.方法用SDS-PAGE和Western blot方法检测63例肺癌及其癌旁组织MAGE-A3抗原的表达情况;用PCR-SSP方法检测70例肺癌及癌旁组织HLA-A1、A2、A24的分布频率.结果 63例肺癌患者中有31例为MAGE-A3抗原表达阳性,其中5例癌旁组织MAGE-A3抗原也为阳性.70例肺癌患者中HLA-A1、A2、A24三个等位基因的分布频率分别为4.28%、54.28%、50.0%;70例癌旁组织中HLA-A1、A2和A24的阳性率分别为4.28%、60.0%和52.86%.三等位基因中任一基因在肺癌组织出现的频率为80%.结论肺癌患者中大约有39%的个体能应用基于MAGE-A3抗原蛋白的肿瘤疫苗进行有效的肿瘤免疫治疗.

  2. HLA antigens in chronic inflammatory demyelinating polyneuropathy.

    OpenAIRE

    Feeney, D J; Pollard, J D; McLeod, J G; Stewart, G. J.; Doran, T J

    1990-01-01

    HLA typing of 71 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) showed an overall increase in frequencies of HLA-A3, -B7, -DR2 as well as concomitantly decreased frequencies of HLA-44 and DR7. The strongest associations were seen with HLA-DR2, -DR7 and -B44 in CIDP overall, although they did not reach statistical significance.

  3. Generation of functional HLA-DR*1101 tetramers receptive for loading with pathogen or tumour derived synthetic peptides

    Directory of Open Access Journals (Sweden)

    Protti Maria

    2005-12-01

    Full Text Available Abstract Background MHC class I-peptide tetramers are currently utilised to characterize CD8+ T cell responses at single cell level. The generation and use of MHC class II tetramers to study antigen-specific CD4+ T cells appears less straightforward. Most MHC class II tetramers are produced with a homogeneously built-in peptide, reducing greatly their flexibility of use. We attempted the generation of "empty" functional HLA-DR*1101 tetramers, receptive for loading with synthetic peptides by incubation. No such reagent is in fact available for this HLA-DR allele, one of the most frequent in the Caucasian population. Results We compared soluble MHC class II-immunoglobulin fusion proteins (HLA-DR*1101-Ig with soluble MHC class II protein fused with an optimised Bir site for enzymatic biotynilation (HLA-DR*1101-Bir, both produced in insect cells. The molecules were multimerised by binding fluorochrome-protein A or fluorochrome-streptavidin, respectively. We find that HLA-DR*1101-Bir molecules are superior to the HLA-DR*1101-Ig ones both in biochemical and functional terms. HLA-DR*1101-Bir molecules can be pulsed with at least three different promiscuous peptide epitopes, derived from Tetanus Toxoid, influenza HA and the tumour associated antigen MAGE-3 respectively, to stain specific CD4+ T cells. Both staining temperature and activation state of CD4+ T cells are critical for the binding of peptide-pulsed HLA-DR*1101-Bir to the cognate TCR. Conclusion It is therefore possible to generate a soluble recombinant HLA-DR*1101 backbone that is receptive for loading with different peptides to stain specific CD4+ T cells. As shown for other HLA-DR alleles, we confirm that not all the strategies to produce soluble HLA-DR*1101 multimers are equivalent.

  4. Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules

    KAUST Repository

    Magnacca, A.

    2012-07-17

    Nascent HLA-class I molecules are stabilized by proteasome-derived peptides in the ER and the new complexes proceed to the cell surface through the post-ER vesicles. It has been shown, however, that less stable complexes can exchange peptides in the Trans Golgi Network (TGN). HLA-B27 are the most studied HLA-class I molecules due to their association with Ankylosing Spondylitis (AS). Chimeric proteins driven by TAT of HIV have been exploited by us to deliver viral epitopes, whose cross-presentation by the HLA-B27 molecules was proteasome and TAP-independent and not restricted to Antigen-Presenting Cells (APC). Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. We found that the antigen presentation by the two HLA-B27 molecules was proteasome-, TAP-, and APC-independent whereas the presentation by the HLA-A2 molecules required proteasome, TAP and professional APC. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. The results showed that this mutation did not influence the HLA-A2-restricted antigen presentation while it drastically affected the HLA-B27-restricted presentation with, however, remarkable differences between B*2705 and B*2709. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67S-B*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes.

  5. Identification of class II ADP-ribosylation factors as cellular factors required for hepatitis C virus replication.

    Science.gov (United States)

    Farhat, Rayan; Séron, Karin; Ferlin, Juliette; Fénéant, Lucie; Belouzard, Sandrine; Goueslain, Lucie; Jackson, Catherine L; Dubuisson, Jean; Rouillé, Yves

    2016-08-01

    GBF1 is a host factor required for hepatitis C virus (HCV) replication. GBF1 functions as a guanine nucleotide exchange factor for G-proteins of the Arf family, which regulate membrane dynamics in the early secretory pathway and the metabolism of cytoplasmic lipid droplets. Here we established that the Arf-guanine nucleotide exchange factor activity of GBF1 is critical for its function in HCV replication, indicating that it promotes viral replication by activating one or more Arf family members. Arf involvement was confirmed with the use of two dominant negative Arf1 mutants. However, siRNA-mediated depletion of Arf1, Arf3 (class I Arfs), Arf4 or Arf5 (class II Arfs), which potentially interact with GBF1, did not significantly inhibit HCV infection. In contrast, the simultaneous depletion of both Arf4 and Arf5, but not of any other Arf pair, imposed a significant inhibition of HCV infection. Interestingly, the simultaneous depletion of both Arf4 and Arf5 had no impact on the activity of the secretory pathway and induced a compaction of the Golgi and an accumulation of lipid droplets. A similar phenotype of lipid droplet accumulation was also observed when GBF1 was inhibited by brefeldin A. In contrast, the simultaneous depletion of both Arf1 and Arf4 resulted in secretion inhibition and Golgi scattering, two actions reminiscent of GBF1 inhibition. We conclude that GBF1 could regulate different metabolic pathways through the activation of different pairs of Arf proteins. PMID:26814617

  6. Association of HLA-DQ with Idiopathic Dilated Cardiomyopathy in a Northern Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    WeiLiu; WeiminLi; NinglingSun

    2004-01-01

    Autoimmune mechanisms are likely involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) and components of MHC may serve as markers for the propensity to develop immune-mediated myocardial damage. This study was conducted to investigate the possible association between HLA-DQA1, -DQB1 alleles and IDC in Han population from northern China by using PCR-based sequence-specific primer (PCR-SSP) technique for HLA genotyping. Among 68 unrelated IDC patients, 4 probands of IDC pedigrees and 100 healthy controls, we found that the alleles of HLA-DQAI*0501 and HLA-DQBI*0303 conferred susceptibility to IDC while HLA-DQAI*0201 and HLA-DQBI*0502, *0504 alleles were in negative association with IDC. The serine at position 57 (SERs7) in the exon of HLA-DQBI*0502 and *0504 was confirmed in our experiment as a marker for resistance to IDC. The results suggest that HLA-DQ polymorphism may be involved in the pathogenesis of IDC. Cellular & Molecular Immunology.

  7. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  8. HIV subtype influences HLA-B*07:02-associated HIV disease outcome

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; Adland, Emily; Koyanagi, Madoka;

    2014-01-01

    Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA......-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C......-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than...

  9. Heterogeneity of HLA genetic factors in IDDM susceptibility.

    Science.gov (United States)

    Martell, M; Marcadet, A; Moine, A; Boitard, C; Deschamps, I; Dausset, J; Bach, J F; Cohen, D

    1990-01-01

    The association of certain HLA-D alleles with insulin-dependent diabetes mellitus (IDDM) is well known. One hundred and sixty-one non-related diabetic individuals and 142 non-related healthy controls were typed for the HLA DR-DQw-Dw association, using a restriction fragment length polymorphism (RFLP) typing method that combines three probe/enzyme systems: DRB/Taq I, DQB/Taq I, and DQB/Bam HI. Comparison of frequencies in both diabetics and controls confirms previous results in terms of HLA class II and IDDM association. Moreover, we have found that DR3/3 heterozygous individuals are more susceptible to IDDM when they are also Dw25 (associated with B18) than when they are Dw24 (associated with B8). Using oligonucleotide dot-blot hybridizations we analyzed the HLA-DQB1 sequence of DR3,Dw24 and DR3,Dw25 homozygous individuals, and we found no difference at position 57 between these two DR3-carrying haplotypes. This observation points to the heterogeneity of HLA genetic factors in IDDM susceptibility. PMID:1970333

  10. The Impact of HLA-E Polymorphisms in Graft-versus-Host Disease following HLA-E Matched Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ehteramolsadat Hosseini

    2012-03-01

    Full Text Available The  non-classical MHC  class-I mainly involves in the  regulation of  innate  immune responses where HLA-E  plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated the effect of HLA-E polymorphisms on post-hematopoietic stem cell transplantation outcomes.The study group included 56 donor-patient pairs with underlying malignant hematological disorders undergoing HLA-E  matched allogeneic hematopoietic stem cell transplantation. They were genotyped for HLA-E locus using a sequence specific primer-polymerase chain reaction. The  median follow-up was 20.6 months  (range 0.2-114.8 and  the  parameters assessed were acute and chronic graft-versus-host disease and overall survival.We showed a lower frequency of acute graft-versus-host disease (grade II or more; p=0.02and chronic graft-versus-host disease (extensive; p=0.04 in the patients with HLA- E*0103/0103 genotype compared to other genotypes of HLA-E. There was also an association between HLA-E*0103/0103 and improved overall survival (p=0.001.Conclusively, our  results  suggest a  protective  role  for  HLA-E*0103/0103  genotypeagainst acute graft-versus-host disease (grade II or more and chronic graft-versus-host disease (extensive as well as an association between this genotype and a better overall survival after HLA-E matched allogeneic hematopoietic stem cell transplantation.

  11. Loss of heterozygosity, a frequent but a non-exclusive mechanism responsible for HLA dysregulation in non-Hodgkin's lymphomas

    NARCIS (Netherlands)

    Drenou, B; Tilanus, M; Semana, G; Alizadeh, M; Birebent, B; Grosset, JM; Dias, P; van Wichen, D; Arts, Y; De Santis, D; Fauchet, R; Amiot, L

    2004-01-01

    The frequent alteration of human leucocyte antigen (HLA) class I molecule expression observed in non-Hodgkin's lymphomas (NHL), similarly to solid tumours, has been reported to favour tumoral escape from the immune system. In order to identify the underlying mechanisms, we analysed 15 HLA defective

  12. Propiedades moleculares e inmunológicas de HLA-B14 y su papel en la espondilitis anquilosante

    OpenAIRE

    Merino Rodríguez, Elena

    2008-01-01

    The association of HLA-B27 with ankylosing spondylitis (AS) is the strongest one between an HLA class I molecule and any disease. HLA-B*1403 was strongly associated to AS in the Togolese population, where both this disease and HLA-B27 are unfrequent. B*1402, which differs from B*1403 only at residue 156 (L156R), was found only in the healthy controls. Thus, the availability of two closely related HLAB14 molecules differentially associated with AS, allowed us for the first time ...

  13. Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells

    Science.gov (United States)

    De Ambrosis, Alessandro; Banelli, Barbara; Pira, Giuseppina Li; Aresu, Ottavia; Romani, Massimo; Ferrini, Silvano; Accolla, Roberto S.

    2008-01-01

    The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA-II) molecules after IFN-γ treatment. Here, we report a variant of THP-1 that does not express HLA-II after IFN-γ. The variant's HLA-II phenotype is constant over time in culture and it is not related to a defective IFN-γ-signalling pathway. Transfection of CIITA, the HLA-II transcriptional activator, under the control of a cytomegalovirus promoter rescues high level of HLA-DR surface expression in the variant indicating that the biosynthetic block resides in the expression of CIITA and not in the CIITA-dependent transactivation of the HLA-II promoters. Treatment of the variant with 5-azacytidine (5-aza), which inhibits CpG methylation, restores inducibility of HLA-II by IFN-γ both at transcriptional and phenotypic level and antigen presenting and processing function of the variant. DNA studies demonstrate that the molecular defect of the THP-1 variant originates from the methylation of the CIITA promoter IV. Furthermore, treatment with 5-aza produces a substantial demethylation of CIITA promoter IV and a significant increase of IFN-γ-dependent HLA-II expression in another myelomonocytic cell line, U937. Therefore hyper-methylation of CIITA promoter IV may be a relevant mechanism of epigenetic control preventing HLA-II IFN-γ inducibility in the myelomonocytic cell lineage. PMID:18829986

  14. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K;

    1985-01-01

    .1 and P greater than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced...... of age matched healthy individuals. Treatment with IFN-alpha caused a significant redistribution of mononuclear cells resulting in both absolute and relative lymphopenia. Pre-treatment lymphocyte counts were 1.09 X 10(9)/1 (range 0.49-1.73), post-treatment counts were 0.55 X 10(9)/1 (range 0.39-1.06)....

  15. Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?

    Science.gov (United States)

    Windsor, L; Puschendorf, M; Allcock, R; Scott, A; Sayer, D; Kucharzak, R; Gut, I; McCann, V; Davis, E; Witt, C; Christiansen, F; Price, P

    2005-06-01

    Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC. PMID:15858601

  16. Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage

    OpenAIRE

    Chopera, Denis R; Woodman, Zenda; Mlisana, Koleka; Mlotshwa, Mandla; Martin, Darren P.; Seoighe, Cathal; Treurnicht, Florette; de Rosa, Debra Assis; Hide, Winston; Karim, Salim Abdool; Gray, Clive M.; Williamson, Carolyn; ,

    2008-01-01

    Author Summary Following infection with HIV, it is well established that a person's genetic makeup is a major determinant of how quickly they will progress to AIDS. Particularly important is the class I Human leukocyte antigen (HLA) gene that is responsible for alerting the immune system to HIV's presence. One of the reasons our immune systems are unable to beat HIV is that the virus can mutate to forms that our HLA genes no longer recognise. However, some people have versions of the HLA gene...

  17. A peptide-binding assay for the disease-associated HLA-DQ8 molecule

    DEFF Research Database (Denmark)

    Straumfors, A; Johansen, B H; Vartdal, F;

    1998-01-01

    The study of peptide binding to HLA class II molecules has mostly concentrated on DR molecules. Since many autoimmune diseases show a primary association to particular DQ molecules rather than DR molecules, it is also important to study the peptide-binding properties of DQ molecules. Here we report...... panel of 43 peptides of different lengths and sequences. The DQ8 molecules showed a different pattern of peptide binding compared to a previously studied DQ2 molecule. Peptides derived from thyroid peroxidase, HLA-DQ(alpha1*0301), HLA-DQ(alpha1*0302), retinol receptor and p21ras were among the high...

  18. Associação entre HLA e leucemia em uma população brasileira de etnia mista Association between HLA and leukemia in a mixed Brazilian population

    Directory of Open Access Journals (Sweden)

    Lúcia Aparecida Barion

    2007-06-01

    Full Text Available OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda, 50 com LMA (leucemia mielóide aguda e 78 com LMC (leucemia mielóide crônica. MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers, ambas da One Lambda (Canoga Park, CA, US. RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95%IC = 0,94-10,44; P = 0,03; OR = 3,61; 95%IC = 0,47-27,64, respectivamente, quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95%IC = 1,25-4,67 foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95%IC = 1,46-7,40 e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95%IC = 1,36-3,46 e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95%IC = 1,34-4,16 foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia, 50 with AML (acute myeloid leukemia and 78 with CML (chronic myeloid leukemia. METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers (One Lambda, Canoga Park, CA, USA. RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95%IC = 0.94-10.44; P = 0.03; OR = 3.61; 95%IC = 0.47-27.64, respectively, than in controls. In patients with AML, the

  19. Analyse des HLA de classe II dans la polyarthrite rhumatoïde (PR): rôles dans la susceptibilité et la sévérité de la maladie

    OpenAIRE

    Stingelin, Sibylle; Guerne, Pierre-André

    2005-01-01

    Le diagnostic de polyarthrite rhumatoïde débutante, mais surtout la prédiction de son évolution, restent un défi pour le clinicien. Les patients qui vont développer une forme sévère de la maladie devraient bénéficier d'une prise en charge agressive et la difficulté consiste à les dépister précocement. Il manque en effet de bons facteurs pronostiques. Nous avons analysé la distribution de l'épitope et du DERAA chez des patients PR et des témoins ainsi que le polymorphisme de HLA-DQ *0301 et *0...

  20. Analyse des HLA de classe II dans la polyarthrite rhumatoïde (PR) : rôles dans la susceptibilité et la sévérité de la maladie

    OpenAIRE

    Stingelin, Sibylle

    2003-01-01

    Le diagnostic de polyarthrite rhumatoïde débutante, mais surtout la prédiction de son évolution, restent un défi pour le clinicien. Les patients qui vont développer une forme sévère de la maladie devraient bénéficier d'une prise en charge agressive et la difficulté consiste à les dépister précocement. Il manque en effet de bons facteurs pronostiques. Nous avons analysé la distribution de l'épitope et du DERAA chez des patients PR et des témoins ainsi que le polymorphisme de HLA-DQ *0301 et *0...

  1. Association of Helicobacter pylori with HLA-DR antigen expression in gastritis.

    OpenAIRE

    Wee, A; Teh, M; Kang, J Y

    1992-01-01

    AIMS: To assess the association between Helicobacter pylori-associated gastritis and HLA-DR antigen (class II antigen) expression. METHODS: Fifty endoscopic gastric biopsy specimens were studied for the presence of H pylori, degree and type of inflammation, and for HLA-DR antigen expression in the epithelium. The cases were chosen to represent different categories: inflamed gastric mucosa with (n = 13) and without (n = 20) H pylori, and non-inflamed mucosa (n = 17). RESULTS: The antigen was a...

  2. Prevalence of HLA-B27 in Patients with Ankylosing Spondylitis in Qatar

    OpenAIRE

    M. H. Abdelrahman; Mahdy, S.; I. A. Khanjar; A. M. Siam; H. A. Malallah; S. A. Al-Emadi; Sarakbi, H. A.; M. Hammoudeh

    2012-01-01

    Background and Objectives. The human leukocyte antigen HLA-B27 is a class 1 antigen of the major histocompatibility complex and is strongly associated with ankylosing spondylitis (AS). The purpose of the present study is to investigate the distribution of HLA-B27 in patients with AS of different ethnic groups in Qatar. Design and Setting. Study design was cross-sectional and the setting was rheumatology clinics of Hamad General Hospital in Qatar where most of ankylosing spondylitis patien...

  3. Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

    OpenAIRE

    Viana, H.; F. Nolasco; Santos, MC; Carvalho, F.; Galvão, MJ; Santos, AR; Bordalo, J; Ribeiro Santos, J

    2009-01-01

    BACKGROUND: Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking. MATERIALS AND METHODS: Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed ...

  4. Extended LTA, TNF, LST1 and HLA gene haplotypes and their association with rubella vaccine-induced immunity.

    Directory of Open Access Journals (Sweden)

    Inna G Ovsyannikova

    Full Text Available BACKGROUND: Recent studies have suggested the importance of HLA genes in determining immune responses following rubella vaccine. The telomeric class III region of the HLA complex harbors several genes, including lymphotoxin alpha (LTA, tumor necrosis factor (TNF and leukocyte specific transcript -1 (LST1 genes, located between the class I B and class II DRB1 loci. Apart from HLA, little is known about the effect of this extended genetic region on HLA haplotypic backgrounds as applied to immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We examined the association between immune responses and extended class I-class II-class III haplotypes among 714 healthy children after two doses of rubella vaccination. These extended haplotypes were then compared to the HLA-only haplotypes. The most significant association was observed between haplotypes extending across the HLA class I region, ten-SNP haplotypes, and the HLA class II region (i.e. A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1-DPA1-DPB1 and rubella-specific antibodies (global p-value of 0.03. Associations were found between both extended A*02-C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p = 0.002 and HLA-only A*02-C*03-B*15-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes (p = 0.009 and higher levels of rubella antibodies. The class II HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p = 0.04 lacking LTA-TNF-LST1 SNPs was associated with lower rubella antibody responses. Similarly, the class I-class II HLA-only A*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02-DPA1*01-DPB1*04 haplotype was associated with increased TNF-alpha secretion levels (p = 0.009. In contrast, the extended AAAACGGGGC-DRB1*01-DQA1*01-DQB1*05-DPA1*01-DPB1*04 (p = 0.01 haplotype was found to trend with decreased rubella-specific IL-6 secretion levels. CONCLUSIONS/SIGNIFICANCE: These data suggest the importance of examining both HLA genes and genes in the class III region as part of the extended haplotypes useful in

  5. Separate developmental programs for HLA-A and -B cell surface expression during differentiation from embryonic stem cells to lymphocytes, adipocytes and osteoblasts.

    Directory of Open Access Journals (Sweden)

    Hardee J Sabir

    Full Text Available A major problem of allogeneic stem cell therapy is immunologically mediated graft rejection. HLA class I A, B, and Cw antigens are crucial factors, but little is known of their respective expression on stem cells and their progenies. We have recently shown that locus-specific expression (HLA-A, but not -B is seen on some multipotent stem cells, and this raises the question how this is in other stem cells and how it changes during differentiation. In this study, we have used flow cytometry to investigate the cell surface expression of HLA-A and -B on human embryonic stem cells (hESC, human hematopoietic stem cells (hHSC, human mesenchymal stem cells (hMSC and their fully-differentiated progenies such as lymphocytes, adipocytes and osteoblasts. hESC showed extremely low levels of HLA-A and no -B. In contrast, multipotent hMSC and hHSC generally expressed higher levels of HLA-A and clearly HLA-B though at lower levels. IFNγ induced HLA-A to very high levels on both hESC and hMSC and HLA-B on hMSC. Even on hESC, a low expression of HLA-B was achieved. Differentiation of hMSC to osteoblasts downregulated HLA-A expression (P = 0.017. Interestingly HLA class I on T lymphocytes differed between different compartments. Mature bone marrow CD4(+ and CD8(+ T cells expressed similar HLA-A and -B levels as hHSC, while in the peripheral blood they expressed significantly more HLA-B7 (P = 0.0007 and P = 0.004 for CD4(+ and CD8(+ T cells, respectively. Thus different HLA loci are differentially regulated during differentiation of stem cells.

  6. Research advances of HLA-F%HLA-F研究进展

    Institute of Scientific and Technical Information of China (English)

    徐丹萍; 林爱芬; 颜卫华

    2012-01-01

    人类白细胞抗原(human leucocyte antigen,HLA)复合体是人体中基因多态性最高的基因复合体,其多态性与疾病遗传易感性显著相关.人类白细胞抗原-F (human leucocyte antigen-F,HLA-F)属于非经典HLAI类分子中的一员,与HLA-E、-G在结构上十分相似,具有有限的多态性.近年来多数学者聚焦于HLA-F基因转录及分子表达调控、HLA-F表达与临床相关性及HLA-F抗体研制,且取得了重要成果.就HLA-F的研究进展作一综述.%Human leukocyte antigen complex with the highest gene polymorphisms in human, is significantly associated with genetic susceptibility to diseases. Human leukocyte antigen-F belongs to the non-classical HLA I molecules. HLA-F, HLA-E and HLA-G have a similar structure and a limited polymorphism. In recent years, transcription regulation of HLA-F, expression regulation of HLA-F in cell surface, clinical relevance of HLA-F and the preparation of anti-HLA-F, are widely studied and have achieved important results. In the present review, the research advances on HLA-F are discussed.

  7. Research on the Factors of Class A Lightweight Cellular Concrete%A级轻质蜂窝水泥混凝土影响因素探索

    Institute of Scientific and Technical Information of China (English)

    陈建波; 马红宵; 穆琰; 任晓林; 张志国; 赵风清

    2014-01-01

    A kind of soap powder,interface agent N as the main component of the composite foaming agent was de-veloped.Factors affecting the light honeycomb cement concrete were researched.They are the foam,water feed ratio, cement,fly ash,and the impact of the amount of fiber pilot.The ratio has been optimized.By adj usting the ratio of ce-mentitious materials different density levels of cellular concrete blocks were got.By industrial test and optimize the production process parameters,class A Lightweight cellular concrete optimization ratio was got.The product has been tested to achieve JC 1062-2007"foam concrete block"FCB A0.5 B03 product rating,fire rating to A-level.%开发出一种以皂粉、界面剂 N等为主要组分的复合发泡剂,在其基础上开展轻质蜂窝水泥混凝土影响因素试验,对泡沫、水料比、水泥、粉煤灰、纤维的用量及影响进行试验研究,得到优化的配比,通过调整胶凝材料的配比可以得到不同密度等级的蜂窝混凝土砌块。通过工业化试验,优化生产工艺参数,得到 A 级轻质蜂窝水泥混凝土优化配比。产品经检测达到JC 1062-2007《泡沫混凝土砌块》FCB A0.5 B03产品等级,防火等级达到 A级。

  8. HLA-DRB GENES POLYMORPHISM IN CHINESE NORTHERN PATIENTS WITH ATOPIC ASTHMA

    Institute of Scientific and Technical Information of China (English)

    高金明; 林耀广; 邱长春; 马毅

    1998-01-01

    Objective. Atopie asthma provides a usetul model for evaluating the genetic tactors that control human immune responsiveness. HLA class Ⅱ gene products are involved in the control of immune response. As HLA-DRB gene is the most polymorphic HLA class Ⅱ gene, we investigated whether susceptibility or resistance to the disease is associated with HLA-DRB. Methods. Blood samples were obtained from two groups of unrelated Chinese northern adults: (1) 50 atopic asthma (7 of them with familial aggregation) ; (2) 80 healthy controls without asthma or atopy and other HLA-associated diseases. Genomic DNA was extracted from peripheral venous blood leucocytes. The polymorphie second exon of HLA-DRB gene was amplified by sequence-specific primer polymerase chain reaction (SSP/PCR) methods. All patients had their serum IgE(total and spscifie) antibody levels by RAST, bronchial reactivity assessed by methaeholine brocho-provocation test and/or hronchodilation test. Results.There was an increased gene frequency of DR52 and DR52 in asthmatic subjects compared with healthy subjects(17% vs 4.3%, P<0. 01% 50% vs 17.5%, P<0. 01), and the decreased frequency of DR2(15) and DR52 in asthmatic patients(7% vs 18%, P<0. 05; 2% vs 33%, P<0. 01). We found the positive association between DR5(13)-DR52 and sIgE antibody responsiveness to d1 (from house dust mite allergen ); negative association between HLA-DRB alleles and TIgE or BHR ( bronchial hyperresponsiveness). Conclusion. The results suggested that HLA haplotype DR6(13)-DR52 was significantly implicated in suseeptibility to house dust mite induced-asthma, at least it would he more closely assocaated with atopic asthms. Conversely, alleles DR2(15) and DR51 might corder protection against the disease. HLA-DRB genes were particularly involved in regulating human atopie immune response in asthma.

  9. Role of HLA Adaptation in HIV Evolution

    Science.gov (United States)

    Kløverpris, Henrik N.; Leslie, Alasdair; Goulder, Philip

    2016-01-01

    Killing of HIV-infected cells by CD8+ T-cells imposes strong selection pressure on the virus toward escape. The HLA class I molecules that are successful in mediating some degree of control over the virus are those that tend to present epitopes in conserved regions of the proteome, such as in p24 Gag, in which escape also comes at a significant cost to viral replicative capacity (VRC). In some instances, compensatory mutations can fully correct for the fitness cost of such an escape variant; in others, correction is only partial. The consequences of these events within the HIV-infected host, and at the population level following transmission of escape variants, are discussed. The accumulation of escape mutants in populations over the course of the epidemic already shows instances of protective HLA molecules losing their impact, and in certain cases, a modest decline in HIV virulence in association with population-level increase in mutants that reduce VRC. PMID:26834742

  10. Establishment of HLA-DR4 transgenic mice for the identification of CD4+ T cell epitopes of tumor-associated antigens.

    Directory of Open Access Journals (Sweden)

    Junji Yatsuda

    Full Text Available Reports have shown that activation of tumor-specific CD4(+ helper T (Th cells is crucial for effective anti-tumor immunity and identification of Th-cell epitopes is critical for peptide vaccine-based cancer immunotherapy. Although computer algorithms are available to predict peptides with high binding affinity to a specific HLA class II molecule, the ability of those peptides to induce Th-cell responses must be evaluated. We have established HLA-DR4 (HLA-DRA*01:01/HLA-DRB1*04:05 transgenic mice (Tgm, since this HLA-DR allele is most frequent (13.6% in Japanese population, to evaluate HLA-DR4-restricted Th-cell responses to tumor-associated antigen (TAA-derived peptides predicted to bind to HLA-DR4. To avoid weak binding between mouse CD4 and HLA-DR4, Tgm were designed to express chimeric HLA-DR4/I-E(d, where I-E(d α1 and β1 domains were replaced with those from HLA-DR4. Th cells isolated from Tgm immunized with adjuvant and HLA-DR4-binding cytomegalovirus-derived peptide proliferated when stimulated with peptide-pulsed HLA-DR4-transduced mouse L cells, indicating chimeric HLA-DR4/I-E(d has equivalent antigen presenting capacity to HLA-DR4. Immunization with CDCA155-78 peptide, a computer algorithm-predicted HLA-DR4-binding peptide derived from TAA CDCA1, successfully induced Th-cell responses in Tgm, while immunization of HLA-DR4-binding Wilms' tumor 1 antigen-derived peptide with identical amino acid sequence to mouse ortholog failed. This was overcome by using peptide-pulsed syngeneic bone marrow-derived dendritic cells (BM-DC followed by immunization with peptide/CFA booster. BM-DC-based immunization of KIF20A494-517 peptide from another TAA KIF20A, with an almost identical HLA-binding core amino acid sequence to mouse ortholog, successfully induced Th-cell responses in Tgm. Notably, both CDCA155-78 and KIF20A494-517 peptides induced human Th-cell responses in PBMCs from HLA-DR4-positive donors. Finally, an HLA-DR4 binding DEPDC1191

  11. Definition of supertypes for HLA molecules using clustering of specificity matrices

    DEFF Research Database (Denmark)

    Lund, Ole; Nielsen, Morten; Kesmir, Can;

    2004-01-01

    Major histocompatibility complex (MHC) proteins are encoded by extremely polymorphic genes and play a crucial role in immunity. However, not all genetically different MHC molecules are functionally different. Sette and Sidney (1999) have defined nine HLA class I supertypes and showed that with only...... specificities. We report that the previously observed specificities of these class II molecules can be clustered into nine classes, which only partly correspond to the serological classification. We show that classification of HLA molecules may be done in a uniform and automated way. The definition of clusters...

  12. Inhibition of allostimulated HLA-DQ and DP-specific T cells by staphylococcal enterotoxin A

    DEFF Research Database (Denmark)

    Masewicz, S; Ledbetter, J A; Martin, P;

    1993-01-01

    Bacterial superantigens have two immunologically important features. They bind MHC class II molecules and stimulate T cells bearing certain V beta TCR phenotypes. Superantigens such as SEA, SEB, and TSST bind to each of the three HLA class II isotypes (DR, DQ, and DP). Allotypic variation seems to...... play an important role in superantigen binding to class II molecules, but the functional implications of these differences remain largely unknown. In the present investigation, we studied the effects of SEA, SEB, and TSST on allostimulation of HLA-DR-, DQ-, and DP-allospecific T-cell clones. To avoid...

  13. Increased Diversity of the HLA-B40 Ligandome by the Presentation of Peptides Phosphorylated at Their Main Anchor Residue*

    OpenAIRE

    Marcilla, Miguel; Alpízar, Adán; Lombardía, Manuel; Ramos-Fernandez, Antonio; Ramos, Manuel; Albar, Juan Pablo

    2013-01-01

    Human leukocyte antigen (HLA) class I molecules bind peptides derived from the intracellular degradation of endogenous proteins and present them to cytotoxic T lymphocytes, allowing the immune system to detect transformed or virally infected cells. It is known that HLA class I–associated peptides may harbor posttranslational modifications. In particular, phosphorylated ligands have raised much interest as potential targets for cancer immunotherapy. By combining affinity purification with high...

  14. Template Driven Code Generator for HLA Middleware

    NARCIS (Netherlands)

    Jansen, R.E.J.; Prins, L.M.; Huiskamp, W.

    2007-01-01

    HLA is the accepted standard for simulation interoperability. However, the HLA services and the API that is provided for these services are relatively complex from the user point of view. Since the early days of HLA, federate developers have attempted to simplify their task by using middleware that

  15. Influence of HLA-A, HLA-B, and HLA-DR matching on rejection of random corneal grafts using corneal tissue for retrospective DNA HLA typing

    NARCIS (Netherlands)

    M.C. Bartels (Marjolijn); H.G. Otten; B.E. van Gelderen; A. van der Lelij (Allegonda)

    2001-01-01

    textabstractAIM: To establish if coincidental HLA-A, HLA-B, and HLA-DR tissue matching is associated with a reduced likelihood of corneal graft rejection. METHODS: Organ culture preserved random donor corneas were used for penetrating keratoplasty (PKP). Corneal tissue from all gra

  16. Matching for Human Leukocyte Antigens (HLA) in corneal transplantation - to do or not to do.

    Science.gov (United States)

    van Essen, T H; Roelen, D L; Williams, K A; Jager, M J

    2015-05-01

    As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma, rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts. PMID:25601193

  17. Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women

    OpenAIRE

    HASIM, AYSHAMGUL; Abudula, Mangnishahan; Aimiduo, Reshalaiti; Ma, Jun-Qi; JIAO, Zhen; Akula, Gulzareye; Wang, Ting; ABUDULA, ABULIZI

    2012-01-01

    Normal function of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen presentation, mainly due to the deregulation in HLA-I and APM expression or function. The posttranscriptional regulation of HLA-I and APM expression may associate with epigenetic modifications in can...

  18. Cellular and molecular insight into the inhibition of primary root growth of Arabidopsis induced by peptaibols, a class of linear peptide antibiotics mainly produced by Trichoderma spp.

    Science.gov (United States)

    Shi, Wei-Ling; Chen, Xiu-Lan; Wang, Li-Xia; Gong, Zhi-Ting; Li, Shuyu; Li, Chun-Long; Xie, Bin-Bin; Zhang, Wei; Shi, Mei; Li, Chuanyou; Zhang, Yu-Zhong; Song, Xiao-Yan

    2016-04-01

    Trichodermaspp. are well known biocontrol agents that produce a variety of antibiotics. Peptaibols are a class of linear peptide antibiotics mainly produced byTrichoderma Alamethicin, the most studied peptaibol, is reported as toxic to plants at certain concentrations, while the mechanisms involved are unclear. We illustrated the toxic mechanisms of peptaibols by studying the growth-inhibitory effect of Trichokonin VI (TK VI), a peptaibol fromTrichoderma longibrachiatumSMF2, onArabidopsisprimary roots. TK VI inhibited root growth by suppressing cell division and cell elongation, and disrupting root stem cell niche maintenance. TK VI increased auxin content and disrupted auxin response gradients in root tips. Further, we screened theArabidopsisTK VI-resistant mutanttkr1tkr1harbors a point mutation inGORK, which encodes gated outwardly rectifying K(+)channel proteins. This mutation alleviated TK VI-induced suppression of K(+)efflux in roots, thereby stabilizing the auxin gradient. Thetkr1mutant also resisted the phytotoxicity of alamethicin. Our results indicate that GORK channels play a key role in peptaibol-plant interaction and that there is an inter-relationship between GORK channels and maintenance of auxin homeostasis. The cellular and molecular insight into the peptaibol-induced inhibition of plant root growth advances our understanding ofTrichoderma-plant interactions. PMID:26850879

  19. gC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection.

    Science.gov (United States)

    Ghebrehiwet, B; Lim, B L; Kumar, R; Feng, X; Peerschke, E I

    2001-04-01

    as a ligand indicate that both cC1q-R and gC1q-R are co-immunoprecipitated with anti-C1q. Taken together, the evidence accumulated to date supports the concept that in addition to its intracellular localization, gC1q-R is expressed on the cell surface and can serve as a binding site for plasma and microbial proteins, but also challenges the existing paradigm that mitochondrial proteins never leave their designated compartment. It is therefore proposed that gC1q-R belongs to a growing list of a class of proteins initially targeted to the mitochondria but then exported to different compartments of the cell through specific mechanisms which have yet to be identified. The designation 'multifunctional and multicompartmental cellular proteins' is proposed for this class of proteins. PMID:11414365

  20. Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, A.L.; Hughes, M.K. (Pennsylvania State Univ., University Park (United States)); Watkins, D.I. (Univ. of Wisconsin, Madison (United States))

    1993-03-01

    A statistical study of DNA sequences of alleles at the highly polymorphic class I MHC loci of humans, HLA-A and HLA-B, showed evidence of both large-scale recombination events(involving recombination of exons 1-2 of one allele with exons 3-8 of another) and small scale recombination events (involving apparent exchange of short DNA segments). The latter events occurred disproportionately in the region of the gene encoding the antigen recognition site (ARS) of the class I molecule. Furthermore, they involved the ARS codons which are under the strongest selection favoring allelic diversity at the amino acid level. Thus, the frequency of recombinant alleles appears to have been increased by some form of balancing selection (such as overdominant selection) favoring heterozygosity in the ARS. These analyses also revealed a striking difference between the A and B loci. Recombination events appear to have occurred about twice as frequently at the B locus, and recombinants at the B locus were significantly more likely to affect polymorphic sites in the ARS. At the A locus, there are well-defined allelic lineages that have persisted since prior to the human-chimpanzee divergence; but at the B locus, there is no evidence for such long-lasting allelic lineages. Thus, relatively frequent interallelic recombination has apparently been a feature of the long-term evolution of the B locus but not of the A locus. 45 refs., 4 figs., 5 tabs.

  1. An integrated genotyping approach for HLA and other complex genetic systems.

    Science.gov (United States)

    Nelson, Wyatt C; Pyo, Chul-Woo; Vogan, David; Wang, Ruihan; Pyon, Yoon-Soo; Hennessey, Carly; Smith, Anajane; Pereira, Shalini; Ishitani, Akiko; Geraghty, Daniel E

    2015-12-01

    Clinical immunogenetics laboratories performing routine sequencing of human leukocyte antigen (HLA) genes in support of hematopoietic cell transplantation are motivated to upgrade to next-generation sequencing (NGS) technology by its potential for cost savings as well as testing accuracy and flexibility. While NGS machines are available and simple to operate, there are few systems available that provide comprehensive sample preparation and data analysis workflows to complete the process. We report on the development and testing of the Integrated Genotyping System (IGS), which has been designed to specifically address the challenges associated with the adoption of NGS in clinical laboratories. To validate the system for a variety of sample DNA sources, we have tested 336 DNA specimens from whole blood, dried blood spots, buccal swabs, and lymphoblastoid cell lines. HLA class I and class II genotypes were derived from amplicon sequencing of HLA-A, -B, -C for exons 1-7 and HLA-DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4, -DRB5 for exons 1-4. Additionally, to demonstrate the extensibility of the IGS to other genetic loci, KIR haplotyping of 93 samples was carried out in parallel with HLA typing using a workflow based on the HLA system. These results are discussed with respect to their applications in the clinical setting and consequent potential for advancing precision medicine. PMID:26027777

  2. Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome

    Directory of Open Access Journals (Sweden)

    Daiana Landenberger de Carvalho

    2012-01-01

    Full Text Available OBJECTIVE: This study aimed to verify the association between human leukocyte antigens and the bcr-abl fusion protein resulting from t(9;22(q34;q11 in chronic leukemia myeloid and acute lymphoblastic leukemia patients. METHODS: Forty-seven bcr-abl positive individuals were evaluated. Typing was performed bymicrolymphocytotoxicity and molecular biological methods (human leukocyte antigens Class I and Class II. A control group was obtained from the data of potential bone marrow donors registered in the Brazilian Bone Marrow Donor Registry (REDOME. RESULTS: Positive associations with HLA-A25 and HLA-B18 were found for the b2a2 transcript, as well as a tendency towards a positive association with HLA-B40 and a negative association with HLA-A68. The b3a2 transcript showed positive associations with HLA-B40 and HLA-DRB1*3. CONCLUSION: The negative association between human leukocyte antigens and the BCR-ABL transcript suggests that binding and presentation of peptides derived from the chimeric protein are effective to increase a cytotoxic T lymphocyte response appropriate for the destruction of leukemic cells.

  3. Association between HLA-DR1 and -DR3 antigens and unexplained repeated miscarriage

    DEFF Research Database (Denmark)

    Christiansen, O B; Ring, Mette; Rosgaard, A;

    1999-01-01

    antigens--other studies have been unable to demonstrate such associations. For the present meta-analysis, 18 cross-sectional or case-control studies (published or unpublished) reporting on frequencies of HLA-DR1 and -DR3 antigens among Caucasian women with unexplained repeated miscarriage were identified......Few, mostly small, studies have investigated the distribution of HLA class II antigens among women with unexplained recurrent miscarriage. Although some studies have reported statistically significant associations between this syndrome and certain HLA-DR antigens--especially the -DR1 and -DR3...... patients and because patients with only two miscarriages were included in many studies; this is defined as repeated miscarriage. The odds ratios of repeated miscarriage for the HLA-DR1 and -DR3 antigens were calculated for the individual studies and subsequently the pooled odds ratios for the studies were...

  4. Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA.

    Directory of Open Access Journals (Sweden)

    Kouyuki Hirayasu

    Full Text Available Cerebral malaria is a major, life-threatening complication of Plasmodium falciparum malaria, and has very high mortality rate. In murine malaria models, natural killer (NK cell responses have been shown to play a crucial role in the pathogenesis of cerebral malaria. To investigate the role of NK cells in the developmental process of human cerebral malaria, we conducted a case-control study examining genotypes for killer immunoglobulin-like receptors (KIR and their human leukocyte antigen (HLA class I ligands in 477 malaria patients. We found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was significantly associated with the development of cerebral malaria when compared with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52-6.48, P = 0.00079, corrected P = 0.02. In contrast, no other KIR-HLA pairs showed a significant association with cerebral malaria, suggesting that the NK cell repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional responses that facilitate development of cerebral malaria. Furthermore, the frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower in malaria high-endemic populations. These results suggest that natural selection has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high-endemic populations because of the propensity of interaction between KIR2DL3 and C1 to favor development of cerebral malaria. Our findings provide one possible explanation for KIR-HLA co-evolution driven by a microbial pathogen, and its effect on the global distribution of malaria, KIR and HLA.

  5. HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells.

    Science.gov (United States)

    Nattermann, Jacob; Nischalke, Hans Dieter; Hofmeister, Valesko; Kupfer, Bernd; Ahlenstiel, Golo; Feldmann, Georg; Rockstroh, Jiirgen; Weiss, Elisabeth H; Sauerbruch, Tilman; Spengler, Ulrich

    2005-01-01

    HIV has evolved several strategies to evade recognition by the host immune system including down-regulation of major histocompatibility complex (MHC) class I molecules. However, reduced expression of MHC class I molecules may stimulate natural killer (NK) cell lysis in cells of haematopoietic lineage. Here, we describe how HIV counteracts stimulation of NK cells by stabilizing surface expression of the non-classical MHC class I molecule, HLA-E. We demonstrate enhanced expression of HLA-E on lymphocytes from HIV-infected patients and show that in vitro infection of lymphocytes with HIV results in up-regulation of HLA-E expression and reduced susceptibility to NK cell cytotoxicity. Using HLA-E transfected K-562 cells, we identified the well-known HIV T-cell epitope p24 aa14-22a as a ligand for HLA-E that stabilizes surface expression of HLA-E, favouring inhibition of NK cell cytotoxicity. These results propose HIV-mediated up-regulation of HLA-E expression as an additional evasion strategy targeting the antiviral activities of NK cells, which may contribute to the capability of the virus in establishing chronic infection. PMID:15751767

  6. The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA haplotypes.

    Science.gov (United States)

    Kralovicova, J; Marsh, S G E; Waller, M J; Hammarstrom, L; Vorechovsky, I

    2002-09-01

    Here we correct the nucleotide sequence of a single known variant of the HLA-DRA gene. We show that the coding regions of the HLA-DRA*0101 and HLA-DRA*0102 alleles do not differ at two codons as reported previously, but only in codon 217. Using nucleotide sequencing and DNA samples from individuals homozygous in the major histocompatibility complex, we found that the variant, leucine 217-encoding HLA-DRA*0102 allele was present on the haplotypes HLA-B*0801, DRB1*03011, DQB1*0201 (ancestral haplotype AH8.1), HLA-B*07021, DRB1*15011, DQB1*0602 (AH7.1), HLA-B*1501, DRB1*15011, DQB1*0602, HLA-B*1501, DRB1*1402, DQB1*03011 and HLA-A3, B*07021, DRB1*1301, DQB1*0603. The HLA-DRA*0101 allele coding for valine 217 was observed on the haplotypes HLA-B*5701, DRB1*0701, DQB1*03032 (AH57.1), HLA-DRB1*04011, DQB1*0302, HLA-DRB1*0701, DQB1*0202, and HLA-DRB1*0101, DQB1*05011. PMID:12445311

  7. HLA Evolved规范研究分析%Research and Analysis of HLA Evolved Specification

    Institute of Scientific and Technical Information of China (English)

    钟蔚; 龚建兴; 郝建国; 黄柯棣

    2011-01-01

    As the next generation HLA specification which is about to accepted by IEEE,HLA Evolved stands for a newest road ahead for HLA.By comparing HLA 1516-2000 with HLA Evolved,important technical innovation and great changes were summarized and analyzed,which discovered that HLA Evolved had a more powerful function and more strengthen mechanism than HLA 1516-2000.Then,a initial research was put forward on how to develop and immigrate federates under HLA Evolved,being a good start for applying and spreading of HLA Evolved.%HLA Evolved作为即将被IEEE通过和接受的下一代HLA规范,代表了HLA体系的最新发展方向。综合比较了HLA 1516-2000与HLA Evolved,概括分析了模块化FOM、动态库兼容API、智能更新率降低、容错处理、Web支持的HLA等重大技术改进和主要变动,揭示了HLA Evolved更为强大的功能和更加健壮的机制。初步研究了HLA Evolved下成员开发和移植工作,为HLAEvolved规范的应用和推广奠定了基础。

  8. Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia

    Directory of Open Access Journals (Sweden)

    Seik-Soon Khor

    2013-04-01

    Full Text Available Essential hypersomnia (EHS, a sleep disorder characterized by excessive daytime sleepiness, can be divided into two broad classes based on the presence or absence of the HLA-DQB1*06:02 allele. HLA-DQB1*06:02-positive EHS and narcolepsy with cataplexy are associated with the same susceptibility genes. In contrast, there are fewer studies of HLA-DQB1*06:02 negative EHS which, we hypothesized, involves a different pathophysiological pathway than does narcolepsy with cataplexy. In order to identify susceptibility genes associated with HLA-DQB1*06:02 negative EHS, we conducted a genome-wide association study (GWAS of 125 unrelated Japanese EHS patients lacking the HLA-DQB1*06:02 allele and 562 Japanese healthy controls. A comparative study was also performed on 268 HLA-DQB1*06:02 negative Caucasian hypersomnia patients and 1761 HLA-DQB1*06:02 negative Caucasian healthy controls. We identified three SNPs that each represented a unique locus— rs16826005 (P = 1.02E-07; NCKAP5, rs11854769 (P = 6.69E-07; SPRED1, and rs10988217 (P = 3.43E-06; CRAT that were associated with an increased risk of EHS in this Japanese population. Interestingly, rs10988217 showed a similar tendency in its association with both HLA-DQB1*06:02 negative EHS and narcolepsy with cataplexy in both Japanese and Caucasian populations. This is the first GWAS of HLA-DQB1*06:02 negative EHS, and the identification of these three new susceptibility loci should provide additional insights to the pathophysiological pathway of this condition.

  9. HLA typing in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    M. Faré

    2011-09-01

    Full Text Available Objective: the aim of the study was to investigate the relationship between Systemic Sclerosis (SSc and HLA antigens, and to correlate these antigens with the clinical manifestations of the disease. Materials and methods: 55 patients were stratified according a to the cutaneous involvement b to the positivity of Scl- 70 and anticentromere antibody and c to the internal organ involvement, in particular we used HRCT to demonstrate lung fibrosis, echocardiography for the diagnosis of pulmonary hypertension, blood creatinine, urinalysis and arterial hypertension to demonstrate renal failure, and esophagus double-countrast barium swallow for the diagnosis of esophagopathy. The control group consisting of 2000 healthy Caucasian subjects was recruited from the same population. Results: the frequency of the antigens A23 (p=0.003, RR=3.69, B18 (p<0.0001, RR=3.57, and DR11 (p<0.0001, RR=6.18 was statistically increased in the patients population compared with the healthy controls. Although there is no any significant correlation between HLA antigens and different clinical subsets of scleroderma, antigens B18 and DR11 could be associated with more severe clinical features. Conclusions: the presence of a significant association between SSc and specific HLA antigens (A23, B18, and DR11 could link the HLA system with SSc.

  10. HLA typing with monoclonal antibodies: evaluation of 356 HLA monoclonal antibodies including 181 studied during the 10th International Histocompatibility Workshop.

    Science.gov (United States)

    Colombani, J; Lepage, V; Raffoux, C; Colombani, M

    1989-08-01

    During the 10th International Histocompatibility Workshop (10th WS), 181 HLA MoAbs were studied using lymphocytotoxicity micro-technique (LCT) and/or enzyme immuno-assay (EIA), and their capacity to serve as typing reagents was evaluated. 129 MoAbs were tested by both techniques. Results obtained with 92 class I and 86 class II polymorphic MoAbs (10th WS) were compared to published data concerning 180 class I and 176 class II polymorphic MoAbs, listed in an HLA-MoAbs Register maintained in our laboratory. The following conclusions can be proposed: 1/HLA-A, B typing by LCT with MoAbs is possible for about 14 specificities. Some specificities are clearly recognized (HLA-A3, B8, B13, Bw4, Bw6), others are recognized as cross-reacting groups (B7+27+w22+40), others are not currently recognized by any MoAb with restricted specificity (B5, B15). Several MoAbs confirmed the existence of shared epitopes between products from a single locus (A2-A28, A25-A32), or from A and B loci (A2-B17, Bw4-A9-A32). A single HLA-Cw MoAb has been described. 2/HLA class II typing by LCT with MoAbs is more difficult than class I typing. DR2, DR3, DR4, DR5 and DR7 as well as DRw52 and DRw53 are well defined; other DR specificities are poorly or not at all defined. Particular associations (DR1+DR4, DR3+DRw6, all DR except DR7) are recognized by several MoAbs. All DQw specificities are well recognized, including new specificities defined only by MoAbs: WA (DQw4), TA10 (DQw7), 2B3 (DQw6+w8+w9). Only two HLA-DP MoAbs have been described. 3/Satisfactory results, similar to those of LCT, were obtained with EIA using lymphoid cell lines as targets. 4/Human MoAbs (12 in the Register) are satisfactory typing reagents. They could represent in the future a significant contribution to HLA typing with MoAbs. PMID:2609328

  11. DNA typing for HLA-DPB1*02 and -DPB1*04 in multiple sclerosis and juvenile rheumatoid arthritis

    DEFF Research Database (Denmark)

    Fugger, L; Ryder, L P; Morling, N;

    1990-01-01

    arthritis (PJRA), and in 38 patients with multiple sclerosis (MS). Increased frequencies of the cellularly defined HLA-DPw2 in PJRA and of HLA-DPw4 in MS have previously been reported. In the patient groups, the frequencies of the DPB1*02 and DPB1*04 variants did not differ significantly from those expected...... based on the cellularly defined HLA-DP types of the patients and the frequencies of the DPB1*02 and DPB1*04 variants among healthy Danes.......DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes (SSOP) has recently been reported. The amplification step may be specific for the HLA-DPB locus, or it may be specific for one or a group of HLA-DPB alleles, thus increasing the discriminatory...

  12. HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (χ2 = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, χ2 = 4.057, P = 0.044).Conclusion HLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.

  13. Transfusion Related Acute Lung Injury (TRALI) Caused by Red Blood Cell Transfusion Involving Residual Plasma Anti-HLA Antibodies: A report on two Cases and General Considerations

    OpenAIRE

    Olivier Garraud; Léna Absi; Danielle Rebibo; Jean-Yves Muller; Patricia Fromont; Evelyne Voitellier; Marie-Françoise Raynal; Philippe Verdier; Soizick Ducroz; Pascale Ruyer-Dumontier; Fabienne Quainon; Hélène Odent-Malaure

    2005-01-01

    TRALI is considered a serious hazard among immune complications of blood transfusion and its occurrence is admitted to be globally underestimated. Each type of blood product is likely to cause TRALI. We report here on two consecutive observations of TRALI caused by red blood cell concentrates, in which anti-HLA class I and class II antibodies resulting from post-gravitational allo-immunization were evidenced in donors. HLA class...

  14. Identification and distribution of three serologically undetected alleles of HLA-DR by oligonucleotide x DNA typing analysis

    International Nuclear Information System (INIS)

    Recent progress in the molecular biology of human major histocompatibility complex class II genes (HLA-DP, -DQ, -DR) have shown that the genetic complexity and allelic polymorphism are greater than expected. In the case of HLA-DR, three DR β-chain loci have been identified and linked, two of which (DR βI and DR βIII, now assigned names HLA-DR1B and HLA-DR3B) are functional. The authors have shown that the HLA micropolymorphism detected at the DNA sequence level can easily be analyzed by hybridization with allele-specific oligonucleotides (HLA oligotyping). In the case of the HLA DRw52 supertypic specificity, which includes the DR3, DR5, DRw6, and DRw8 haplotypes, three alleles, referred to as DRw52a, DRw52b, and DRw52c, have recently been identified at the HLA-DR3B locus by DNA sequencing. Hybridization with locus- and allele-specific oligonucleotide probes (designated 52a, 52b, and 52c) has been performed on DNA from normal individuals forming a panel of 82 haplotypes to establish the distribution of these three alleles. Individuals of the DR3 haplotype had either the DRw52a or DRw52b allele, and individuals of extended haplotype HLA-A1,B8,DR3 had only the DRw52a allele. DR5 individuals all had the DRw52b allele, while individuals of DRw6 haplotype had the DRw52a, -52b, or -52c allele. None of these three alleles are found in DRw8 individuals. Analysis of this micropolymorphism, undetectable by common typing procedures, is therefore now operational for more accurate HLA matching for transplantation and for improving correlations between HLA and disease susceptibility

  15. Analysis of Killer Cell Immunoglobulin-like Receptor Genes and Their HLA Ligands in Iranian Patients with Ankylosing Spondylitis.

    Science.gov (United States)

    Mahmoudi, Mehdi; Jamshidi, Ahmad Reza; Karami, Jafar; Mohseni, Alireza; Amirzargar, Ali Akbar; Farhadi, Elham; Ahmadzadeh, Nooshin; Nicknam, Mohammad Hossein

    2016-02-01

    Ankylosing Spondylitis (AS) is a chronic rheumatic disease which mainly involves the axial skeleton. It seems that non-HLA genes, as well as HLA-B27 gene, are linked to the etiology of the disease. Recently, it has been documented that KIRs and their HLA ligands are contributed to the Ankylosing Spondylitis. The aim of this study was to evaluate the KIR genes and their HLA ligands in Iranian AS patients and healthy individuals. The present study includes 200 AS patient samples and 200 healthy control samples. KIR genotyping was performed using the polymerase chain reaction sequence-specific primer (PCR-SSP) method to type the presence or absence of the 16 KIR genes, 6 known specific HLA class I ligands and also, two pseudogenes. Two KIR genes (KIR-2DL3 and KIR2DL5), and among the HLA ligands, two HLA ligands (HLA-C2Lys80 and HLA-B27) genes were significantly different between case and control groups. In addition, we found some interesting KIR/HLA compound genotypes, which were associated with AS susceptibility. Our results suggest that the AS patients present more activating and less inhibitory KIR genes with combination of their HLA ligands than healthy controls. Once the balance of signal transduction between activating and inhibitory receptors is disturbed, the ability of NK cells to identify and lyse the targets in immune responses will be compromised. Accordingly, imbalance of activating and inhibitory KIR genes by up-regulating the activation and losing the inhibition of KIRs signaling or combination of both might be one of the important factors which underlying the pathogenesis of AS. PMID:26996109

  16. Usage of Conventional PCR Technology for the Detection of HLA-B27 Allele: A Significant Molecular Marker of Ankylosing Spondylitis

    OpenAIRE

    Sharma, Narotam; Sharma, Veena; Masood, Tariq; Nautiyal, Satish Chandra; Sailwal, Shivani; Singh, Rajesh K.; Kushwaha, Rajeev K.; R. K. Singh

    2012-01-01

    Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukocyte antigen class I allele HLA-B27. More than 90 % of patients with ankylosing spondylitis possess the HLA-B27 allele, but only 1 % of people with HLA-B27 develop the disease. Ankylosing spondylitis predominately affects young males. The present study was planned to find out the involvement of HLA-B27 specific allele in relation to age and sex in symptomatic suspected patients of ankylosing spondy...

  17. The P9 pocket of HLA-DQ2 (non-Aspbeta57) has no particular preference for negatively charged anchor residues found in other type 1 diabetes-predisposing non-Aspbeta57 MHC class II molecules

    DEFF Research Database (Denmark)

    Quarsten, H; Paulsen, G; Johansen, B H;

    1998-01-01

    Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno......-pathogenic peptides. Recent studies in man and mouse have revealed that some type 1 diabetes-predisposing non-Aspbeta57 class II molecules (i.e. DQ8, DR4Dw15 and I-Ag7) preferentially bind peptides with a negatively charged anchor residue at P9. It has been suggested that this is a common feature of type 1 diabetes......-predisposing class II molecules. The molecular explanation for such a phenomenon could be that class II beta chains with Aspbeta57 form a salt bridge between Aspbeta57 and a conserved Arg of the a chain, whereas in non-Aspbeta57 molecules the Arg is unopposed and free to interact with negatively charged P9 peptide...

  18. Multi-population classical HLA type imputation.

    Directory of Open Access Journals (Sweden)

    Alexander Dilthey

    Full Text Available Statistical imputation of classical HLA alleles in case-control studies has become established as a valuable tool for identifying and fine-mapping signals of disease association in the MHC. Imputation into diverse populations has, however, remained challenging, mainly because of the additional haplotypic heterogeneity introduced by combining reference panels of different sources. We present an HLA type imputation model, HLA*IMP:02, designed to operate on a multi-population reference panel. HLA*IMP:02 is based on a graphical representation of haplotype structure. We present a probabilistic algorithm to build such models for the HLA region, accommodating genotyping error, haplotypic heterogeneity and the need for maximum accuracy at the HLA loci, generalizing the work of Browning and Browning (2007 and Ron et al. (1998. HLA*IMP:02 achieves an average 4-digit imputation accuracy on diverse European panels of 97% (call rate 97%. On non-European samples, 2-digit performance is over 90% for most loci and ethnicities where data available. HLA*IMP:02 supports imputation of HLA-DPB1 and HLA-DRB3-5, is highly tolerant of missing data in the imputation panel and works on standard genotype data from popular genotyping chips. It is publicly available in source code and as a user-friendly web service framework.

  19. Inefficient assembly limits transport and cell surface expression of HLA-Cw4 molecules in C1R.

    Science.gov (United States)

    Zemmour, J

    1996-12-01

    HLA-C antigens are expressed to the cell surface at roughly 10% the level of HLA-B or -A, and their serological definition remains persistently difficult. To characterize the factors limiting surface expression, the processes of assembly and intracellular transport of HLA-Cw4 molecules were investigated in the C1R cell line. When appropriate peptides were added to cultured cells or in cell lysates significant amounts of conformed HLA-C molecules that associate with beta 2-microglobulin (beta 2 m) are detected, but are indeed not sufficient to restore expression to the level observed for HLA-A or -B molecules. Furthermore, a precursor/product relationship exists between the free class I heavy chain and the mature conformation of HLA-Cw4 molecules. Thus, HLA-C assembly promotes the conversion of HC-10-reactive molecules (weakly-beta 2m-associated non-ligand associated free HC form) into the beta 2m-associated class I molecules recognized by W6/32. To further investigate the factors that regulate cell surface expression, intracellular transport of HLA-Cw4 was studied in pulse chase analysis. In contrast to some HLA-A and B, maturation of HLA-Cw4 heavy chains and their export to the medial and trans-Golgi compartments are quite inefficient. After 4 h of chase period, roughly half of the pulse-labeled HLA-Cw4 molecules have transited to the medial-Golgi and acquired complex oligosaccharides characteristic of mature form. In addition, treatment with gamma-interferon does not appear to improve maturation of HLA-Cw4 heavy chains, suggesting that increased supply of peptides does not influence intracellular transport. Moreover, only a small fraction in the pool of HLA-Cw4 molecules was subsequently transported through the trans-Golgi network, as indicated by their acquisition of sialic acids. Taken together these studies show that HLA-Cw4 molecules are inefficiently transported through the Golgi apparatus and presumably retained in the endoplasmic reticulum or cis

  20. [Genetic aspects in multiple sclerosis. II: HLA system].

    Science.gov (United States)

    De Rezende, P A; Arruda, W O

    1996-09-01

    Review of studies about HLA antigens and multiple sclerosis (MS). The HLA system, in special class II antigens, subregions DR and DQ, is probably involved in the immunopathogenesis of MS. Haplotype DRB1*1501.DQA1*0102.DQB1*0602, corresponding to phenotype DR2.Dw2.DQ6, is positively associated with MS in several caucasoid populations. Clinical heterogeneity of MS, as well as different diagnostic criteria adopted by investigators are potential sources of confusion and may lead to discrepant results. A better standardization of clinical and laboratorial methodology, appropriate subdivision of patients with different clinical forms of MS, may allow a more accurate evaluation of the role of genetic factors in the pathogenesis of MS. PMID:9109989

  1. Detecting Site-Specific Physicochemical Selective Pressures: Applications to the Class I HLA of the Human Major Histocompatibility Complex and the SRK of the Plant Sporophytic Self-Incompatibility System

    DEFF Research Database (Denmark)

    Sainudiin, Raazesh; Wong, Wendy Shuk Wan; Yogeeswaran, Krithika;

    2005-01-01

    :transversion biases. Here, we apply this method to two positively selected receptors involved in ligand-recognition: the class I alleles of the human major histocompatibility complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous...

  2. Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains

    DEFF Research Database (Denmark)

    Dellgren, Christoffer; Nehlin, Jan O; Barington, Torben

    2015-01-01

    . Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly......Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses...... expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of...

  3. Aspectos genéticos da esclerose múltipla: II. sistema HLA Genetic aspects in multiple sclerosis: HLA system

    OpenAIRE

    Patrícia Almeida de Rezende; Walter Oleschko Arruda

    1996-01-01

    Foi feita análise e revisão de estudos populacionais de associação entre antígenos HLA e a esclerose múltipla (EM). Há evidências de que os genes HLA, principalmente os de classe II, das sub-regiões DR e DQ possam estar envolvidos. O haplótipo DRB1*1501.DQA1*0102.DQB1*0602 referente ao fenótipo DR2.Dw2.DQ6 foi encontrado em associação positiva em vários estudos realizados em populações caucasóides. O desequilíbrio de ligação entre os genes DR e DQ dificulta o reconhecimento da contribuição in...

  4. HLA-A*0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins

    International Nuclear Information System (INIS)

    The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N) and spike (S) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of HLA-A2.1 transgenic mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla_bind/), ten each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays, with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to be First identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein. In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our identified N317-325 and S1042-1050 CTL epitopes could induce recall responses when IFN-γ stimulation of blood CD8+ T-cells revealed significant difference between normal healthy donors and SARS-recovered patients after those PBMCs were in vitro vaccinated with their cognate antigen. Our results would provide a new insight into the development of therapeutic vaccine in SARS

  5. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

    Science.gov (United States)

    Romanos, Jihane; Rosén, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; van Heel, David A; Cukrowska, Bozena; Bruno, Valentina; Mazzilli, Maria Cristina; Núñez, Concepcion; Bilbao, Jose Ramon; Mearin, M Luisa; Barisani, Donatella; Rewers, Marian; Norris, Jill M; Ivarsson, Anneli; Boezen, H Marieke; Liu, Edwin; Wijmenga, Cisca

    2014-01-01

    Background The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case–control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD. PMID:23704318

  6. Assessing high affinity binding to HLA-DQ2.5 by a novel peptide library based approach

    DEFF Research Database (Denmark)

    Jüse, Ulrike; Arntzen, Magnus; Højrup, Peter;

    2011-01-01

    Here we report on a novel peptide library based method for HLA class II binding motif identification. The approach is based on water soluble HLA class II molecules and soluble dedicated peptide libraries. A high number of different synthetic peptides are competing to interact with a limited amount...... of HLA molecules, giving a selective force in the binding. The peptide libraries can be designed so that the sequence length, the alignment of binding registers, the numbers and composition of random positions are controlled, and also modified amino acids can be included. Selected library peptides...... bound to HLA are then isolated by size exclusion chromatography and sequenced by tandem mass spectrometry online coupled to liquid chromatography. The MS/MS data are subsequently searched against a library defined database using a search engine such as Mascot, followed by manual inspection of the...

  7. Association of class II human histocompatibility leukocyte antigens with rheumatic fever.

    OpenAIRE

    Ayoub, E M; Barrett, D J; Maclaren, N K; Krischer, J P

    1986-01-01

    The association of class I and II HLA antigens with rheumatic fever and its manifestations was examined in 72 patients, including 48 blacks and 24 Caucasians. No significant association was found between class I antigens and rheumatic fever. In contrast, HLA-DR2 and HLA-DR4 phenotypes were encountered in a significantly higher frequency in black and Caucasian patients with rheumatic fever, respectively, compared with the control populations (P less than 0.005). The most significant associatio...

  8. The role of soluble HLA-G and HLA-G receptors in patients with hematological malignancies after allogeneic stem cell transplantation.

    Science.gov (United States)

    Biedroń, Monika; Rybka, Justyna; Wróbel, Tomasz; Prajs, Iwona; Poręba, Rafał; Kuliczkowski, Kazimierz

    2015-08-01

    HLA-G is a non-classical MHC class I molecule whose suppressive activity on immune effector cells is exerted due to interactions with receptors ILT2, ILT4 and KIR2DL4. These receptors are expressed mainly on NK cells and monocytes, and their intensity of expression changes depending on HLA-G level. HLA-G plays an important role in the development of tolerance following organ transplantations and bone marrow stem cell transplantations. HLA-G also participates in the modulation of the immune response during cancerogenesis. The aim of this study was to assess HLA-G level in blood serum, the percentage of NK cells and monocytes with expression of receptors for HLA-G (ILT2, ILT4, KIR2DL4 and NKG2D) in patients who received allogeneic stem cell transplantations, and their influence on the occurrence of graft-versus-host reaction. The study included 32 patients with bone marrow diseases (acute leukemias, myelodysplastic syndrome, chronic myeloid leukemia, paroxysmal nocturnal hemoglobinuria) who received allogeneic stem cell transplantations. We assessed the expression of receptors ILT2, ILT4, KIR2DL4 and NKG2D on monocytes and NK cells, as well as the level of HLA-G in blood serum in patients before conditioning, in the transplant hematopoietic reconstitution period following allogeneic bone marrow stem cell transplantation. The percentage of NK cells with expression of KIR2DL4, ILT2 and ILT4 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The percentage of monocytes with expression of ILT4 and ILT2 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The level of HLA-G in patients' blood serum was higher after the stem cell transplantation compared with the period before transplantation. HLA-G level and HLA-G receptors are related to intensity of GVHD and may play the role of a prognostic factor for the development of GVHD and the clinical course of this reaction. PMID:26187179

  9. The IMGT/HLA sequence database.

    Science.gov (United States)

    Robinson, J; Marsh, S G

    2000-01-01

    The IMGT/HLA database (wwwebi.ac.uk/imgt/hla/) specialises in sequences of the polymorphic genes of the HLA system, the humanmajor histocompatibility complex (MHC). This complex is located within the 6p213 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and these include the 21 highly polymorphic HLA genes, which influence the outcome of clinical transplantation and confer susceptibility to a wide range of non-infectious diseases. The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools, and detailed descriptions of the source cells. The online submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. The latest version (release 1.10.0 April 2001) contains 1329 HLA alleles, 61 HLA related sequences, derived from around 3350 component sequences from the EMBL/ GenBank/DDBJ databases. The IMGT/HLA database provides a model that will be extended to provide specialist databases for polymorphic MHC genes of other species. PMID:12361093

  10. Complement activation and HLA-B27.

    OpenAIRE

    Meri, S.; Partanen, J; Leirisalo-Repo, M; Repo, H

    1988-01-01

    The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopoly...

  11. Derivation of HLA types from shotgun sequence datasets

    OpenAIRE

    Warren, Rene; Choe, Gina; Freeman, Douglas; Castellarin, Mauro; Munro, Sarah; Moore, Richard; Holt, Robert

    2012-01-01

    The human leukocyte antigen (HLA) is key to many aspects of human physiology and medicine. All current sequence-based HLA typing methodologies are targeted approaches requiring the amplification of specific HLA gene segments. Whole genome, exome and transcriptome shotgun sequencing can generate prodigious data but due to the complexity of HLA loci these data have not been immediately informative regarding HLA genotype. We describe HLAminer, a computational method for identifying HLA alleles d...

  12. Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT.

    Science.gov (United States)

    Crivello, Pietro; Heinold, Andreas; Rebmann, Vera; Ottinger, Hellmut D; Horn, Peter A; Beelen, Dietrich W; Fleischhauer, Katharina

    2016-07-01

    The role of HLA amino acid (AA) polymorphism for the outcome of hematopoietic cell transplantation (HCT) is controversial, in particular for HLA class II. Here, we investigated this question in nonpermissive HLA-DPB1 T-cell epitope (TCE) mismatches reflected by numerical functional distance (FD) scores, assignable to all HLA-DPB1 alleles based on the combined impact of 12 polymorphic AAs. We calculated the difference in FD scores (ΔFD) of mismatched HLA-DPB1 alleles in patients and their 10/10 HLA-matched unrelated donors of 379 HCTs performed at our center for acute leukemia or myelodysplastic syndrome. Receiver-operator curve-based stratification into 2 ΔFD subgroups showed a significantly higher percentage of nonpermissive TCE mismatches for ΔFD >2.665, compared with ΔFD ≤2.665 (88% vs 25%, P 2.665 was significantly associated with overall survival (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.05-1.87; P TCE mismatches. There was a marked but not statistically significant increase in the hazards of relapse and nonrelapse mortality in the high ΔFD subgroup, whereas no differences were observed for acute and chronic graft-versus-host disease. Seven nonconservative AA substitutions in peptide-binding positions had a significantly stronger impact on ΔFD compared with 5 others (P = .0025), demonstrating qualitative differences in the relative impact of AA polymorphism in HLA-DPB1. The novel concept of ΔFD sheds new light onto nonpermissive HLA-DPB1 mismatches in unrelated HCT. PMID:27162243

  13. Alteration of HLA-B27 Peptide Presentation after Infection of Transfected Murine L Cells by Shigella flexneri

    OpenAIRE

    Boisgérault, Florence; Mounier, Joëlle; Tieng, Vannary; Stolzenberg, Marie-Claude; Khalil-Daher, Iman; Schmid, Michel; Sansonetti, Philippe; Charron, Dominique; Toubert, Antoine

    1998-01-01

    Shigella flexneri is a triggering agent for reactive arthritis in HLA-B27-susceptible individuals. Considering the intracellular multiplication of bacteria, it seems likely that bacterial peptides may be presented by the major histocompatibility complex (MHC) class I pathway. To examine this hypothesis, we infected HLA-B*2705- and/or human β2-microglobulin-transfected murine L-cell lines with M90T, an invasive strain of S. flexneri. Bacterial infection induced no detectable modifications in t...

  14. Soluble HLA-G Molecules Are Increased during Acute Leukemia, Especially in Subtypes Affecting Monocytic and Lymphoid Lineages1

    OpenAIRE

    Gros, Frédéric; Sebti, Yasmine; de Guibert, Sophie; Branger, Bernard; Bernard, Marc; Fauchet, Renée; Amiot, Laurence

    2006-01-01

    Human leukocyte antigen G (HLA-G) molecules corresponding to nonclassic class I genes of the major histocompatibility complex exhibit immunomodulatory properties. They are either membrane-bound or solubly expressed during certain tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G) molecules seem more frequently expressed than membrane-bound isoforms during hematologic malignancies, such as lymphoproliferative disorders. Assay of these molecules by enzyme-linked immunosorbent assa...

  15. Soluble HLA-G Molecules Are Increased during Acute Leukemia, Especially in Subtypes Affecting Monocytic and Lymphoid Lineages'

    OpenAIRE

    Frédéric Gros; Yasmine Sebti; Sophie de Guiber; Bernard Branger; Marc Bernard; Renée Fauchet; Laurence Amiot

    2006-01-01

    Human leukocyte antigen G (HLA-G) molecules corresponding to nonclassic class I genes of the major histocompatibility complex exhibit immunomodulatory properties. They are either membrane-bound or solubly expressed during certain tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G) molecules seem more frequently expressed than membranebound isoforms during hematologic malignancies, such as lymphoproliferative disorders. Assay of these molecules by enzyme-linked immunosorbent assay...

  16. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease.

    Science.gov (United States)

    Levinson, Ralph D; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki; Rajalingam, Raja

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  17. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease

    Science.gov (United States)

    Levinson, Ralph D.; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher’s exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  18. Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors.

    Directory of Open Access Journals (Sweden)

    Adiba Isa

    Full Text Available HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced a 9-42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8(+ T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types.

  19. Correlation of Cecal Microflora of HLA-B27 Transgenic Rats with Inflammatory Bowel Disease

    OpenAIRE

    Onderdonk, Andrew B; Richardson, James A.; Hammer, Robert E.; Taurog, Joel D.

    1998-01-01

    Transgenic rats with a high level of expression of the human major histocompatibility complex class I molecule HLA-B27 develop chronic inflammatory bowel disease (IBD) and arthritis. Assessment of the cecal microflora showed a rise in numbers of Escherichia coli and Enterococcus spp., corresponding to the presence and severity of IBD in these rats.

  20. Cellular expression or binding of desLys58-beta2 microglobulin is not dependent on the presence of the tri-molecular MHC class I complex

    DEFF Research Database (Denmark)

    Wang, M; Corlin, D B; Heegaard, N H H; Claesson, M H; Nissen, Mogens Holst

    2008-01-01

    significantly increased when cells were pre-incubated with dbeta2m and when TIB-202 cells were exposed to lipopolysaccharide. dbeta2m was also expressed on T leukaemic Jurkat cells as well as on low HLA-expressing erythroleukaemic K562 cells. beta2m gene-deleted murine splenocytes only bound 332-01 after pre......The monoclonal antibody 332-01 is a newly developed antibody which specifically recognizes human desLys58-beta2 microglobulin (dbeta2m). In the present study, we characterized the binding of 332-01 to peripheral blood mononuclear cells (PBMC), a number of human leukaemic and monocytic cell lines......, and beta2m gene-deleted murine lymphocytes. dbeta2m was found to be expressed on non-activated and activated monocytes. When cells were pre-exposed to dbeta2m, 332-01 also bound to non-activated T lymphocytes. dbeta2m was expressed on the monocytic cell lines U937 and TIB-202, and binding was...

  1. An HLA based flight simulation architecture

    NARCIS (Netherlands)

    Huiskamp, W.; Jense, G.J.; Janssen, H.G.M.

    2000-01-01

    Modern distributed simulation concepts such as the US DoD High Level Architecture (HLA) support interoperability between heterogeneous simulations, thus enabling the development of flexible, re-usable simulation Federations. Based on the principles of HLA, the Dutch national collaborative project 'S

  2. HLA typing in acute optic neuritis

    DEFF Research Database (Denmark)

    Frederiksen, J L; Madsen, H O; Ryder, L P;

    1997-01-01

    frequency of HLA-DR15 was significantly increased in patients with ON + CDMS (52%) and ON (47%) compared with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON + CDMS (18%), ON (23%), and control (23%) groups. The frequencies of HLA-DQA-1B (55% in ON + CDMS, 58% in ON) and HLA......-DQB-1B (49% in ON + CDMS, 59% in ON) were significantly increased compared with control subjects (41%, HLA-DQA-1B; 37%, HLA-DQB-1B). Brain MRI was abnormal in 48 of 56 examined patients with ON + CDMS and in 64 of 120 examined patients with ON (P < .001). In contrast, the frequencies of HLA alleles did...... not differ between patients with and without demyelinating lesions. However, patients with ON and normal MRI findings did not show association with HLA-DR15. CONCLUSIONS: The frequencies of alleles were similar in patients with ON and ON + CDMS, confirming that they are not 2 immunogenetically...

  3. Technological advances in the study of HLA-DRA promoter regulation: Extending the functions of CIITA, Oct-1, Rb, and RFX

    Institute of Scientific and Technical Information of China (English)

    Melissa I.Niesen; Aaron R.Osborne; William R.Lagor; Harry Zhang; Kristy Kazemfar; Gene C.Ness; George Blanck

    2009-01-01

    Several advances were established in examining the interaction of transcriptional factors with the HLA-DRA promoter. First, hydrodynamic injection was used to demonstrate the activation of the promoter by class II transactivator in a live mouse. Second, the Oct-1 DNA-binding site in the HLA-DRA promoter is a negative element in many cells, but here we show that Oct-1 activates the promoter independently of the Oct-1-binding site. Third, the retinoblastoma (Rb) protein is required for the induction of the endogenous HLA-DRA gene, due to a poorly understood, pleiotropic effect on the Oct-1 and YY1 repressive functions at the HLA-DRA promoter. There has never been an indication that direct promoter activation, by Rb, is possible. Here, we report that the first HLA-DRA intron has an Rb-responsive element, as indicated by a transient transfection/promoter reporter assay. Finally, RFX activates a methylated version of an HLA-DRA promoter reporter construct, consistent with the role of RFX in rescuing the expression of the methylated, endogenous HLA-DRA gene. Here, we report that this RFX function is not limited to a specific RFX-binding sequence or to the HLA-DRA promoter. These advances provide bases for novel investigations into the function of the major histocompatibility class II promoter.

  4. HLA-G in human early pregnancy: Control of uterine immune cell activation and likely

    Directory of Open Access Journals (Sweden)

    Philippe Le Bouteiller

    2015-02-01

    Full Text Available Despite a number of controversies, the functional importance of human leukocyte antigen G (HLA-G in early human pregnancy is now sustained by a large amount of sound data. Membrane-bound and soluble HLA-G isoforms, either as β2-microglobulin-free or -associated as monomers or dimers, are expressed by different trophoblast subpopulations, the only fetal-derived cells that are directly in contact with maternal cells (maternal-fetal interfaces. Trophoblast HLA-G is the specific ligand of multiple cellular receptors present in maternal immune and non-immune cells, including CD8, leukocyte immunoglobulin-like receptor (LILR B1, LILRB2, killer cell immunoglobulin-like receptor (KIR 2DL4, and possibly CD160. Trophoblast HLA-G specific engagement of these cellular receptors triggers either inhibitory or activating signals in decidual CD8 + T cells, CD4 + T cells, natural killer (NK cells, macrophages, dendritic cells, or endothelial cells. Such HLA-G-receptor specific interactions first contribute to limit potentially harmful maternal anti-paternal immune response by impairment of decidual NK cell cytotoxicity, inhibition of CD4 + and CD8 + T-cell and B-cell proliferation, and induction of apoptosis of activated CD8 + T cells. Second, these HLA-G specific interactions contribute to stimulate placental development through secretion of angiogenic factors by decidual NK cells and macrophages, and to provide a protective effect for the outcome of pregnancy by the secretion of interleukin (IL-4 by decidual trophoblast antigen-specific CD4 + T cells.

  5. Association of HLA-DRB1 Alleles with Ulcerative Colitis in the City of Kerman, South Eastern Iran

    Directory of Open Access Journals (Sweden)

    Mojgan Mohammadi

    2015-10-01

    Full Text Available The association of HLA class II genes with ulcerative colitis (UC as an autoimmune disease has been investigated for several years. However, factors responsible for genetic predisposition of this disease have so far not been clearly understood. In this study, for the first time, we aimed to investigate the association between HLA-DRB1 types and UC in the population of Kerman, a city southeast Iran.HLA typing was performed among 85 UC patients and 95 healthy controls using PCRamplification, employing sequence specific primers (PCR-SSP. The DRB1 frequencies were determined in the patients and controls.HLA-DRB1*04 was negatively associated with UC. Furthermore, HLA-DRB1*13 was significantly associated with severity of the disease (p=0.01 among UC patients.This is the novel result that describes an association of HLA-DRB1*13 with UC and also shows the protective role of HLA-DRB1*04 against the disease in people of Kerman.

  6. SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients

    OpenAIRE

    McElroy, JP.; Isobe, N.; Gourraud, PA; Caillier, SJ; Matsushita, T.; Kohriyama, T.; Miyamoto, K; Nakatsuji, Y; Miki, T; Hauser, SL; Oksenberg, JR; KIRA, J

    2011-01-01

    Although several major histocompatibility complex (MHC)-wide single-nucleotide polymorphism (SNP) studies have been performed in populations of European descent, none have been performed in Asian populations. The objective of this study was to identify human leukocyte antigen (HLA) loci associated with multiple sclerosis (MS) in a Japanese population genotyped for 3534 MHC region SNPs. Using a logistic regression model, two SNPs (MHC Class III SNP rs422951 in the NOTCH4 gene and MHC Class II ...

  7. Modeling HLA associations with EBV-positive and -negative Hodgkin lymphoma suggests distinct mechanisms in disease pathogenesis.

    Science.gov (United States)

    Johnson, Paul C D; McAulay, Karen A; Montgomery, Dorothy; Lake, Annette; Shield, Lesley; Gallagher, Alice; Little, Ann-Margaret; Shah, Anila; Marsh, Steven G E; Taylor, G Malcolm; Jarrett, Ruth F

    2015-09-01

    HLA genotyping and genome wide association studies provide strong evidence for associations between Human Leukocyte Antigen (HLA) alleles and classical Hodgkin lymphoma (cHL). Analysis of these associations is complicated by the extensive linkage disequilibrium within the major histocompatibility region and recent data suggesting that associations with EBV-positive and EBV-negative cHL are largely distinct. To distinguish independent and therefore potentially causal associations from associations confounded by linkage disequilibrium, we applied a variable selection regression modeling procedure to directly typed HLA class I and II genes and selected SNPs from EBV-stratified patient subgroups. In final models, HLA-A*01:01 and B*37:01 were associated with an increased risk of EBV-positive cHL whereas DRB1*15:01 and DPB1*01:01 were associated with decreased risk. Effects were independent of a prior history of infectious mononucleosis. For EBV-negative cHL the class II SNP rs6903608 remained the strongest predictor of disease risk after adjusting for the effects of common HLA alleles. Associations with "all cHL" and differences by case EBV status reflected the subgroup analysis. In conclusion, this study extends previous findings by identifying novel HLA associations with EBV-stratified subgroups of cHL, highlighting those alleles likely to be biologically relevant and strengthening evidence implicating genetic variation associated with the SNP rs6903608. PMID:25648508

  8. 麻风病与HLA-A、HLA-B、HLA-DRB1、HLA-DQ等位基因关联性分析%Analysis of the association of HLA-A, HLA-B, HLA-DRB1, HLA-DQ alleles with leprosy

    Institute of Scientific and Technical Information of China (English)

    赵宝泉; 俞宙; 杨菲; 蔡志坚; 周迎; 于德宝; 李娟; 王建莉; 渠鹏程

    2012-01-01

    目的 探讨中国山东人群HLA-A、HLA-B、HLA-DRB1、HLA-DQ等位基因与麻风病的相关性.方法 采用序列特异性引物聚合酶链反应法(PCR-SSP)对40例麻风病患者及20例健康对照者进行HLA-A、B、DRB1、DQ等位基因分型,x2检验基因频率差异.结果 麻风病患者HLA-B*13(x2=7.067,P=0.008)、DQ*02(x2 =4.156,P=0.041)基因频率较健康对照组低,有统计学意义(P<0.05).LL型麻风患者HLA-B* 13(x2=7.159,P=0.007)等位基因频率降低、HLA-DRB1*15(x2=4.073,P=0.044)等位基因频率升高,与健康对照组相比均具有统计学意义(P<0.05).TT型麻风病患者HLA-B *40(P =0.037)、DQ *05(x2 =5.147,P=0.023)等位基因频率高于健康对照组,差异具有统计学意义(P<0.05).结论 HLA-B * 13、DQ*02基因可能对麻风病易感性有拮抗作用,可能是保护基因;HLA-B* 13可能是LL型拮抗基因、DRB1*15可能是LL型的易感基因;HLA-B* 40、DQ *05可能是TT型的易感基因.%Objective To explore the association of HLA-A,HLA-B,HLA-DRB1,HLA-DQ alleles with leprosy in population of Jinan.Methods PCR-SSP was used to analyse the type of HLA-A,HLA-B,HLA-DRB1 and HLA-DQ alleles in 40 patients with leprosy and 20 healthy controls.SPSS 11.5 software package was used to analyze the data.Results The allele frequencies of HLA-B * 13 (x2 =7.067,P =0.008)and DQ * 02 (x2 =4.156,P =0.041 ) were lower in leprosy patients than those in healthy controls( P < 0.05 ).The allele frequencies of HLA-B * 13 (x2 =7.159,P =0.007 )was lower than that in controls and the frequencies of HLA- DRB 1 * 15 (x2 =4.073,P =0.044) was higher in LL leprosy patients ( P < 0.05 ).The allele frequencies of HLA-B * 40 ( P =0.037 ) and DQ * 05 (x2 =5.147,P =0.023 ) were higher in TT leprosy patients (P<0.05).Conclusion HLA-B * 13 and DQ *02 possibly play protective roles in leprosy patients.B * 13 has also protective roles and DRB1 * 15 was a susceptibility gene in LL leprosy patients.B *40,DQ *05 may be

  9. Characterization of a new HLA-B allele (B{sup *}3702) generated by an intronic recombination event

    Energy Technology Data Exchange (ETDEWEB)

    Santos, S.; Vicario, J.L.; Merino, J.L.; Balas, A. [Regional Transfusion Centre, Madrid (Spain)

    1996-12-31

    Routine serological HLA typing of s Syrian family revealed a Bw4-associated HLA-B blank antigen showing Mendelian segregation together with the haplotype A1, Cw2, DR11, DQ7 (a father and one of his children, cells NO. 5958641 and No. 1958125). A more extensive serological analysis was done by using additional polyclonal and monoclonal antibodies (mAb; One-Lambda BL-60 and LM172 plates) as well as the 12th International Workshop class I mAb plate. Both cells showed no conclusive typing reactions with sera towards HLA-B27 and HLA-B37 antigens. Two mAb, PAMELA (27,44,38) and FAY (13,27,37,47), were able to recognize this antigen. The great majority of polyclonal reagents against B37 showed negative reactions, while weak results were frequently observed with anti-B27 allosera. 8 refs., 1 fig., 1 tab.

  10. Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2'-deoxycytidine

    Institute of Scientific and Technical Information of China (English)

    Wei Hua YAN; Ai Fen LIN; Chien Chung CHANG; Soldano FERRONE

    2005-01-01

    The non-classical HLA class I antigen HLA-G is an immune modulator which inhibits the functions of T cells,NK cells,and the Dendritic cells (DC).As a result,HLA-G expression in malignant cells may provide them with a mechanism to escape the immune surveillance.In melanoma,HLA-G antigen expression has been found in 30% of surgically removed lesions but in less than 1% of established cell lines.One possible mechanism underlying the differential HLAG expression in vivo and in vitro is that the HLA-G gene is epigenetically repressed in melanoma cells in vitro.To test this hypothesis,we treated the HLA-G negative melanoma cell line OCM-1A with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AC) and analyzed whether HLA-G expression can be restored.Our data strongly suggest that HLA-G is silenced as a result of CpG hypermethylation within a 5' regulatory region encompassing 220 bp upstream of the start codon.After treatment,HLA-G mRNA expression was dramatically increased.Western blot and flow cytometry showed that HLA-G protein was induced.Interestingly,HLA-G cell surface expression on the 5-AC treated OCM-1A cells is much less than that on the HLA-G positive JEG-3 cells while a similar amount of total HLA-G was observed.Possible mechanisms for the difference were analyzed in the study such as cell cold-treatment,peptide loading and antigen processing machinery components (APM) as well as β2 microglobulin (β2-m) expression.Data revealed that the APM component calreticulin might be involved in the lower HLA-G surface expression on OCM-1A cells.Taken together,our results indicated that DNA methylation is an important epigenetic mechanism by which HLA-G antigen expression is modulated in melanoma cells in vitro. Furthermore,to the first time, we hypothesized that the deficiency of calreticulin might be involved in the low HLA-G surface expression on the 5-AC treated OCM-lA cells.

  11. HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish.

    Science.gov (United States)

    Ross, Owen A; Curran, Martin D; Rea, I Maeve; Hyland, Paul; Duggan, Orla; Barnett, Christopher R; Annett, Kathryn; Patterson, Chris; Barnett, Yvonne A; Middleton, Derek

    2003-04-01

    Polymorphism of the human leukocyte antigen has been implicated in a number of autoimmune disorders including ageing. In the course of the present study, no association of the human leukocyte antigen (HLA)-A1, B8, DR3 haplotype with a male Irish aged population, as previously reported, was observed. Two polymorphic nucleotides in the TNF cluster (G-308A TNF-alpha and G+252A TNF-beta), associated with increased TNF-alpha production, were shown to be in tight linkage disequilibrium with the class I and II HLA loci, generating HLA haplotypes with extended linkage disequilibrium. However, no age-related allele or genotype frequencies were observed for either polymorphic nucleotide. PMID:12714268

  12. The radiographic features of rheumatoid arthritis in HLA-B27-positive patients

    Energy Technology Data Exchange (ETDEWEB)

    Rundback, J.H. (Dept. of Radiology, Beth Israel Medical Center, New York, NY (United States)); Rosenberg, Z.S. (Dept. of Radiology, Hospital for Joint Diseases, Orthopaedic Inst., New York, NY (United States)); Solomon, G. (Dept. of Rheumatology, Hospital for Joint Diseases, Orthopaedic Institute, New York, NY (United States))

    1993-05-01

    Radiographs were reviewed in a group of nine patients with classical seropositive rheumatoid arthritis who on tissue typing were found to express the class I HLA-B27 allele. Radiographs were analyzed with regard to whether or not they demonstrated radiographic features of (1) classical rheumatoid arthritis, (2) seronegative arthritis, or (3) mixed features of rheumatoid and seronegative arthritis. Five patients (55%) displayed radiographic features consistent with a diagnosis of rheumatoid arthritis, two patients (22%) showed radiographic features of seronegative disorder (periostitis and sacroiliitis), and two patients (22%) showed a mixed picture with evidence of both rheumatoid arthritis and a seronegative disorder. Thus, the HLA-B27 allele contributed to the radiographic features in 44% of patients with rheumatoid arthritis and associated HLA-B27. Thus, the wide range of findings in our population indicates that the radiographic attributes are not specific enough to constitute a unique subpopulation of patients with rheumatoid arthritis. (orig.)

  13. Increased Frequency of HLA B 17 Antigen in Girls with Turner Syndrome and their Fathers

    Directory of Open Access Journals (Sweden)

    C. Dacou-Voutetakis

    1993-01-01

    Full Text Available HLA-A, -B and -DR antigen distribution was studied in 49 girls with Turner Syndrome (TS, in 43 of their parents, as well as in 433 controls. No increased frequency of DR3, DR4 was found in our group. However, an increased frequency of HLA B 17 antigen was disclosed (18.3% in TS versus 6.4% in the controls, p<0.001 and Pc<0.01. Furthermore, the HLA B 17 antigen was of paternal origin in 77.7% of the cases . The interpretation of the present findings is quite difficult. Most likely, the findings are related to the chromosomal abnormality rather than to autoimmunity. It is quite possible that genes within the region of class I genes create unfavorable circumstances leading to the loss of the sex chromosome or, alternatively, genes in this region confer protection and prevent miscarriage of the affected fetus.

  14. Induction of HLA-DR antigen on human squamous carcinoma by recombinant interferon gamma.

    Science.gov (United States)

    Koch, W M; Dugan, E; Diaz, L A; Richtsmeier, W J

    1988-05-01

    The antigen recognition system which plays the major role in immunologic attraction mechanisms, including graft rejection, is the class II major histocompatibility complex containing the HLA-DR locus. Few types of cells constitutively express this antigen, as it is a potent immunological activating signal usually confined to antigen processing cells, activated lymphocytes, and endothelium. Using indirect immunofluorescence, we have observed induction of the HLA-DR glycoprotein in selected head and neck squamous cell carcinoma tissue cultures treated with recombinant interferon gamma. This occurs in concert with growth arrest and morphological changes after rHuIFN-gamma treatment. This report describes the induction of a surface antigen that may have profound prognostic significance. Understanding the kinetics of HLA-DR induction will aid in the design and assessment of adoptive immunotherapy with rHuIFN-gamma. PMID:3129628

  15. The radiographic features of rheumatoid arthritis in HLA-B27-positive patients

    International Nuclear Information System (INIS)

    Radiographs were reviewed in a group of nine patients with classical seropositive rheumatoid arthritis who on tissue typing were found to express the class I HLA-B27 allele. Radiographs were analyzed with regard to whether or not they demonstrated radiographic features of (1) classical rheumatoid arthritis, (2) seronegative arthritis, or (3) mixed features of rheumatoid and seronegative arthritis. Five patients (55%) displayed radiographic features consistent with a diagnosis of rheumatoid arthritis, two patients (22%) showed radiographic features of seronegative disorder (periostitis and sacroiliitis), and two patients (22%) showed a mixed picture with evidence of both rheumatoid arthritis and a seronegative disorder. Thus, the HLA-B27 allele contributed to the radiographic features in 44% of patients with rheumatoid arthritis and associated HLA-B27. Thus, the wide range of findings in our population indicates that the radiographic attributes are not specific enough to constitute a unique subpopulation of patients with rheumatoid arthritis. (orig.)

  16. HLA diversity in the 1000 genomes dataset.

    Directory of Open Access Journals (Sweden)

    Pierre-Antoine Gourraud

    Full Text Available The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC, only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.

  17. Nomenclature for factors of the HLA system, 1980*

    OpenAIRE

    1980-01-01

    This article outlines the decisions made by the WHO nomenclature committee on leukocyte antigens at a meeting held after the 8th International Workshop on Histocompatibility Testing. Particular attention is given to new designations for provisional HLA-B and HLA-DR specificities and the upgrading of certain HLA-D and HLA-DR specificities to full HLA status. The existence of supertypic cross-reacting specificities was confirmed and extended.

  18. HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis.

    Science.gov (United States)

    Shimokawa, Paulo Tadashi; Targa, Lília Spaleta; Yamamoto, Lidia; Rodrigues, Jonatas Cristian; Kanunfre, Kelly Aparecida; Okay, Thelma Suely

    2016-05-18

    Host and parasite genotypes are among the factors associated with congenital toxoplasmosis pathogenesis. As HLA class II molecules play a key role in the immune system regulation, the aim of this study was to investigate whether HLA-DQA1/B1 alleles are associated with susceptibility or protection to congenital toxoplasmosis. One hundred and twenty-two fetuses with and 103 without toxoplasmosis were studied. The two study groups were comparable according to a number of socio-demographic and genetic variables. HLA alleles were typed by PCR-SSP. In the HLA-DQA1 region, the allele frequencies showed that *01:03 and *03:02 alleles could confer susceptibility (OR= 3.06, p = 0.0002 and OR= 9.60, p= 0.0001, respectively) as they were more frequent among infected fetuses. Regarding the HLA-DQB1 region, the *05:04 allele could confer susceptibility (OR = 6.95, p toxoplasmosis and the most severe cases has been shown. PMID:26856406

  19. [A monoclonal antibody recognizes a novel HLA-DQ specificity, DQWa].

    Science.gov (United States)

    Ishikawa, N

    1985-09-01

    A monoclonal antibody (MoAb) with a novel DQ specificity has been produced by immunizing a C3H/He mouse with a human B lymphoblastoid cell line EBV-Wa (HLA-Dw 15/DR 4/DQ blank homozygous). The MoAb, termed HU-46, reacts with panel cells associated with HLA-Dw 15/DR 4 and certain panel cells with HLA-Dw 8/DRw 8 specificity, which are typed as DQ blank. Immunochemical analyses indicated that the MoAb recognizes a new class II antigen, which is coded by the HLA-DQ sublocus. In the ninth International Histocompatibility Workshop, three HLA-DQ specificities, DQw 1, DQw 2 and DQw 3, were officially designated. But the DQ specificity detected by HU-46 has not yet been reported. We provisionally named this new DQ specificity DQWa and presumed that it is fourth DQ specificity. Furthermore, in a genetic analysis, assuming the Hardy-Weinberg condition hold, it was confirmed that DQWa is an allele of the three DQ specificities. PMID:2416664

  20. "HUMAN LEUKOCYTE CLASS I AND II ANTIGENS IN IRANIAN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY"

    Directory of Open Access Journals (Sweden)

    "A. Aghamohammadi

    2004-09-01

    Full Text Available Common variable immunodeficiency (CVID is a heterogeneous heritable disease characterized by arrest in B cell differentiation. An association between CVID and two HLA haplotypes, haplotype I (HLA-A1, HLA-B8, HLA-DR3 and haplotype II (HLA-A29, HLA-B44, HLADR7has been previously documented. In the present study, we have attempted to find an association between susceptibility to CVID and HLA class I and II antigens in Iranian population. Seventeen Iranian patients with CVID (mean age 17, range 3-28 years; 12 male and 5 female, including two couples of brothers and 100 healthy controls were studied. All subjects were typed for HLA class 1, and 12 patients and all controls were typed for HLA class II, using microdroplet lymphocytotoxicity technique. Out of 12 CVID patients typed for HLA-DR and DQ specificities, five patients presented DR-1, which showed an increased frequency in patient (41.6% vs. 12% in controls, and 3 presented DQ-2, which also showed an increased frequency (25% vs. 4% in controls, both of which reached statistical significance (P = 0.018 and P = 0.026, respectively. HLA-DR10 was present in 2 patients (16.6%, which was markedly more frequent compared to controls, but this difference was not significant statistically. Our results suggest that HLA-DR1 and DQ-2 may contribute to susceptibility to CVID. We did not find any significant association between HLA-A1, B8 and DR3 that has been previously reported to be associated with CVID.

  1. HLA-B8 association with late-stage melanoma – an immunological lesson?

    Directory of Open Access Journals (Sweden)

    Andersen Mads

    2006-03-01

    Full Text Available Abstract Background Differences in HLA allele frequencies between the diseased and healthy populations may signify efficient immune responses, a notion that has been successfully tested for infectious diseases or for association with genetic elements involved in a distinct type of immunity. This retrospective study is intended to detect differences in MHC class I carrier frequencies of advanced melanoma patients compared to healthy bone marrow donors. Methods The HLA-A and -B carrier frequencies of 748 stage IV melanoma patients retrieved from serotyping at 6 different centers in Germany were compared using a chi-square test to 13,386 fully HLA typed bone marrow donors registered in the German national bone marrow donor registry. Results The comparison of HLA carrier frequencies in advanced cancer patients with healthy bone marrow donors revealed a significant decrease in HLA-B8 carrier frequencies, which was also apparent in patients with advanced disease compared to patients with loco-regional disease. Conclusion The data suggest that protective immune responses restricted to distinct MHC class I molecules may be operational in a subset of melanoma patients, which is the prerequisite for a large scale screen for the corresponding epitopes. Alternatively, the known association of the ancestral haplotype HLA-A1, -B8 and -DR3 with genetic elements such as distinct TNF-α alleles might have a protective effect on disease progression. In any case, identification of the cause of protection within this patient subset might lead to a significant improvement in the efficacy of current immunotherapeutic approaches.

  2. Identification of a new HLA-G allele, HLA-G*01:19, by cloning and phasing.

    Science.gov (United States)

    Wang, W Y; Tian, W

    2016-08-01

    A new HLA-G allelic variant, HLA-G*01:19, was identified in a southern Chinese Han population by polymerase chain reaction-sequence-based typing (PCR-SBT), cloning and phasing. HLA-G*01:19 differs from HLA-G*01:04:01 by a nonsynonymous cytosine at position 99 in exon 2, resulting in amino acid change from valine to leucine at codon 34 of the mature HLA-G molecule. PMID:27277539

  3. Polymorphism in the regulatory region located more than 1.1 kilobases 5' to the start site of transcription, the promoter region, and exon 1 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, Steen; Morling, Niels

    1999-01-01

    The non-classic Human Leucocyte Antigen class Ib molecule, HLA-G, is expressed on the invasive, extra-villous cytotrophoblast in human placenta. HLA-G protects against natural killer (NK)-cell-mediated lysis and may modulate the secretion of cytokines. Aberrant expression of HLA-G has been reported...... can be divided into two groups based on the detected polymorphism. The nucleotide substitutions may have implications for the binding of nuclear factors to the regulatory regions. To our knowledge this is the first study of any polymorphism in the 5'-flanking sequences to the HLA-G gene. Further...

  4. Polymorphism in the regulatory region located more than 1.1 kilobases 5' to the start site of transcription, the promoter region, and exon 1 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, Steen; Morling, N

    1999-01-01

    The non-classic Human Leucocyte Antigen class Ib molecule, HLA-G, is expressed on the invasive, extra-villous cytotrophoblast in human placenta. HLA-G protects against natural killer (NK)-cell-mediated lysis and may modulate the secretion of cytokines. Aberrant expression of HLA-G has been reported...... in certain disorders of pregnancy. We have studied the DNA sequences of the putative regulatory region located more than 1.1 kilobases 5' from the start site of transcription (a 244 bp HindIII/EcoRI fragment) of the HLA-G gene and of the promoter region to detect any possible polymorphism. We...

  5. Quantitative Trait Locus and Brain Expression of HLA-DPA1 Offers Evidence of Shared Immune Alterations in Psychiatric Disorders.

    Science.gov (United States)

    Morgan, Ling Z; Rollins, Brandi; Sequeira, Adolfo; Byerley, William; DeLisi, Lynn E; Schatzberg, Alan F; Barchas, Jack D; Myers, Richard M; Watson, Stanley J; Akil, Huda; Bunney, William E; Vawter, Marquis P

    2016-01-01

    Genome-wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC) were highly significant following genome-wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1) in brain from individual subjects with schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. Exon microarrays were performed in anterior cingulate cortex (ACC) in BD compared to controls, and both HLA-DPA1 and CD74 were decreased in expression in BD. The expression of HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA-DPA1 exons 2-3-4 as suggested by exon microarrays. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL) that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL) by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future tests in a

  6. Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.

    Science.gov (United States)

    Garcia-Beltran, Wilfredo F; Hölzemer, Angelique; Martrus, Gloria; Chung, Amy W; Pacheco, Yovana; Simoneau, Camille R; Rucevic, Marijana; Lamothe-Molina, Pedro A; Pertel, Thomas; Kim, Tae-Eun; Dugan, Haley; Alter, Galit; Dechanet-Merville, Julie; Jost, Stephanie; Carrington, Mary; Altfeld, Marcus

    2016-09-01

    The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease. PMID:27455421

  7. HLA-G1-transfected K562 cells do not inhibit NK-cell-mediated lysis in europium release cytotoxicity assay.

    Science.gov (United States)

    Sapak, M; Buc, M

    2003-01-01

    The class Ia of HLA molecules are recognised by NK-cells either by inhibitory or stimulatory NK-receptors. When inhibitory signals prevail over stimulatoryones, the target cells expressing the class Ia of HLA molecules are not lysed by NK-cells. Similarly, class Ib of HLA molecules have been reported to induce the inhibitory signal in NK-cells. The cell line K562 is deprived of both class Ia and class Ib of HLA molecules, respectively, the fact of which enhances the lysis of K562 cells when they are co-cultivated with NK-cells. To study the role of HLA-G molecules in NK-cell cytotoxic activity, HLA-G tranfected K562 cells were used as target cells. NK-cells were isolated from the peripheral blood of 4 unrelated persons using Miltenyi's Biotec isolation system. The purity of directly isolated NK cells (CD56 Multisort kit) was 74.1%, and that of indirectly isolated NK-cells (NK-cell isolation kit) 69.4%. The europium release cytotoxicity assay was used in all experiments. The percentage of cytotoxicity ranged from 19% to 24% when K562 target cells were used. Similar results were obtained with the HLA-G1-transfected target cells: the percentage of cytotoxicity ranged from 17% to 29%. Our preliminary results indicate that NK-cells are able to lyse both, K562 cells and the HLA-G1-transfected K562 cells. (Tab. 1, Fig. 8, Ref. 21.). PMID:15055728

  8. Seronegative pauciarticular arthritis and HLA B27.

    OpenAIRE

    Eastmond, C J; Rajah, S M; D. Tovey; Wright, V.

    1980-01-01

    Twenty-six patients with a pauciarticular arthritis have been studied clinically, radiologically and with histocompatibility typing. An increased frequency of HLA B27 was found (p = 1.87 x 10(-12)). Low back and buttock pain, Achilles tendinitis and dactylitis of the toes were more frequent in HLA-B27 positive patients. It is suggested that histocompatibility testing may be of some value in diagnosis and in the investigation of the possible 'reactive' nature of this type of arthritis.

  9. Describing the Peptide Binding Specificity of HLA-C

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Harndahl, Mikkel Nors; Nielsen, Morten;

    for 5 HLA-C molecules and for all, but one, molecule we find a high frequency of binders, >70%, among these peptides. To extend the examined peptide space, we use bioinformatic prediction tools to search for additional binders. Finally, we update our prediction tool, NetMHCpan, with the HLA-C affinity......Human leukocyte antigen (HLA) presents peptides to T-cells for immune scrutiny. Whereas HLA-A and -B have been described in great detail, HLA-C has received much less attention. Here, to increase the coverage of HLA-C and the accuracy of the corresponding tools, we have generated HLA-C molecules......; peptide-binding assays, data and predictors; and tetramers; representing the most prevalent HLA-C molecules. We have combined positional scanning combinatorial peptide library (PSCPL) with a homogenous high-throughput dissociation assay and generated specificity matrices for 11 different HLA-C molecules...

  10. HLA-B27 subtypes among the Chukotka native groups

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I. [Akademiya Meditsinskikh Nauk SSSR, Moscow (Russian Federation). Inst. Revmatizma; Reveille, J.D.; Arnett, F.C. [Texas Univ., Houston, TX (United States). Health Science Center

    1995-12-31

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter`s syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs.

  11. Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

    Science.gov (United States)

    Porto dos Santos, Maisa; de Melo Silva, Cláudia Maria; Alves de Almeida, Vanessa; Assumpção Antunes, Irineide

    2016-01-01

    Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1*04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon. The HLA-DRB1*04 was prevalent in patients with pulmonary TB (p<0.0001; OR = 2.94; 95% CI = 2.12 to 4.08). Direct nucleotide sequencing of DRB1 exon 2 identified nine subtypes of HLA-DRB1*04. The subtype HLA-DRB1*04:11:01 (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70) was associated with susceptibility to pulmonary TB while DRB1*04:07:01 (p<0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) to protection. Notably, the interaction between alcohol and HLA-DRB1*04:11:01 increased the risk for developing pulmonary TB (p = 0.0001; OR = 51.3; 95% CI = 6.81 to 386). Multibacillary pulmonary TB, the clinical presentation of disease transmission, was strongly associated with interaction to alcohol (p = 0.0026; OR = 11.1; 95% CI = 3.99 to 30.9), HLA-DRB1*04:11:01 (p = 0.0442; OR = 2.01; 95% CI = 1.03 to 3.93) and DRB1*04:92 (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results show that HLA-DRB1*04 are associated with pulmonary TB. Interestingly, three subtypes, DRB1*04:07:01, DRB1*04:11:01 and DRB1*04:92 of the HLA-DRB1*04 could be potential immunogenetic markers that may help to explain mechanisms involved in disease development. PMID:26901036

  12. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

    Directory of Open Access Journals (Sweden)

    Spaans Vivian M

    2012-09-01

    Full Text Available Abstract Background Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%, followed by adenocarcinoma (AC and adenosquamous carcinoma (ASC; together 15-20%. Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E, a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival. Methods and results HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56% cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; P = 0.010. High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 and P = 0

  13. A comparative review of HLA associations with hepatitis B and C viral infections across global populations

    Institute of Scientific and Technical Information of China (English)

    Rashmi Singh; Rashmi Kaul; Anil Kaul; Khalid Khan

    2007-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance ofchronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  14. Polymorphism of HLA-B27: 105 subtypes currently known.

    Science.gov (United States)

    Khan, Muhammad Asim

    2013-10-01

    HLA-B27 has a high degree of genetic polymorphism, with 105 known subtypes, named HLA-B*27:01 to HLA-B*27:106, encoded by 132 alleles. The most common subtypes associated with ankylosing spondylitis are HLA-B*27:05 (Caucasians), HLA-B*27:04 (Chinese), and HLA-B*27:02 (Mediterranean populations). For Chinese populations, HLA-B*27:04 is associated with a greater ankylosing spondylitis risk than HLA-B*27:05. Two subtypes, HLA-B27*06 and HLA-B27*09, seem to have no disease association. These differential disease associations of HLA-B27 subtypes, and the recent discovery that ERAP1 is associated with ankylosing spondylitis for patients with HLA-B27, have increased attempts to determine the function of HLA-B27 in disease pathogenesis by studying hemodynamic features of its protein structure, alterations of its peptidome, aberrant peptide handling, and associated molecular events. However, after 40 years we still do not fully know how HLA-B27 predisposes to ankylosing spondylitis and related spondyloarthritis. PMID:23990399

  15. Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment

    OpenAIRE

    1993-01-01

    We have previously produced lines of rats transgenic for HLA-B27 and human beta 2-microglobulin (h beta 2m) that develop a progressive inflammatory disease sharing many clinical and histologic features with the B27-associated human spondyloarthropathies, including gut and male genital inflammation, arthritis, and psoriasiform skin lesions. Other transgenic lines that express lower levels of B27 and h beta 2m remain healthy. To investigate the cellular basis for the multisystem inflammatory di...

  16. Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.

    LENUS (Irish Health Repository)

    Fanning, Liam J

    2012-02-03

    The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test. HLA-A, -B, -C allelic group profile was molecularly defined by reverse line probe hybridization. The strongest individual allelic group associations with persistent HCV infection were HLA A*11 (p = 0.044) and Cw*04 (p = 0.006). However, only the HLA C*04 association survived correction for multiple comparisons. Further analysis of alleles in linkage with HLA Cw*04 revealed that the haplotype HLA A*11, Cw*04 was present in 11 individuals, 10 of whom were viremic (p = 0.05). No gene dosage effect was observed. No association between HLA class 1 allelic groups and aviremia and virus load was evident in this white population. HLA B*44 is associated with low virus load in human immunodeficiency virus disease, but this association was not evident in this HCV-infected population. Novel HLA class 1 alleles associated with persistence of HCV have been identified.

  17. HLA-B73: An atypical HLA-B molecule carrying a Bw6-epitope motif variant and a B pocket identical to HLA-B27

    Energy Technology Data Exchange (ETDEWEB)

    Vilches, C.; Pablo, R. de; Herrero, M.J.; Moreno, M.E.; Kreisler, M. [Hospital Puerta de Hierro, Madrid (Spain)

    1994-12-31

    HLA-B73, first described by Mayr and Kirnbauer (1981), is a poorly characterized allospecificity, serologically related to the B7-CREG. We polymerase chain reaction-amplified, cloned and sequenced the HLA-B alleles of the B-LCL LE023, established from a Spanish Caucasoid individual expressing HLA-B73. 5 refs., 2 figs.

  18. Aspectos genéticos da esclerose múltipla: II. sistema HLA Genetic aspects in multiple sclerosis: HLA system

    Directory of Open Access Journals (Sweden)

    Patrícia Almeida de Rezende

    1996-09-01

    Full Text Available Foi feita análise e revisão de estudos populacionais de associação entre antígenos HLA e a esclerose múltipla (EM. Há evidências de que os genes HLA, principalmente os de classe II, das sub-regiões DR e DQ possam estar envolvidos. O haplótipo DRB1*1501.DQA1*0102.DQB1*0602 referente ao fenótipo DR2.Dw2.DQ6 foi encontrado em associação positiva em vários estudos realizados em populações caucasóides. O desequilíbrio de ligação entre os genes DR e DQ dificulta o reconhecimento da contribuição individual de cada alelo. A heterogeneidade de critérios diagnósticos da EM constitui importante fator metodológico que dificulta a comparação entre os diversos estudos. A padronização dos critérios diagnósticos e dos métodos laboratoriais empregados, assim como a análise individual de grupos de pacientes com formas clínicas diferentes, são medidas que provavelmente permitirão avaliação mais precisa dos fatores genéticos envolvidos no desenvolvimento da EM.Review of studies about HLA antigens and multiple sclerosis (MS. The HLA system, in special class II antigens, subregions DR and DQ, is probably involved in the immunopathogenesis of MS. Haplotype DRB1*1501.DQA1*0102.DQB1*0602, corresponding to phenotype DR2.Dw2.DQ6, is positively associated with MS in several caucasoid populations. Clinical heterogeneity of MS, as well as different diagnostic criteria adopted by investigators are potential sources of confusion and may lead to discrepant results. A better standardization of clinical and laboratorial methodology, appropriate subdivision of patients with different clinical forms of MS, may allow a more accurate evaluation of the role of genetic factors in the pathogenesis of MS.

  19. Epistatic Interaction of ERAP1 and HLA-B in Behçet Disease: A Replication Study in the Spanish Population

    OpenAIRE

    Marta Conde-Jaldón; Marco Antonio Montes-Cano; José Raul García-Lozano; Lourdes Ortiz-Fernández; Norberto Ortego-Centeno; Rocío González-León; Gerard Espinosa; Genaro Graña-Gil; Juan Sánchez-Bursón; Miguel Angel González-Gay; Ana Celia Barnosi-Marín; Roser Solans; Patricia Fanlo; Mónica Rodríguez Carballeira; Teresa Camps

    2014-01-01

    Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish populatio...

  20. Analysis of HLA-A, HLA-B, HLA-DRB1 allelic, genotypic, and haplotypic frequencies in colombian population

    Directory of Open Access Journals (Sweden)

    Yazmin Rocío Árias-Murillo

    2010-12-01

    Full Text Available Introduction: The high polymorphism of the HLA system allows its typification to be used as valuable tool in establishing association to various illnesses, immune and genetic profiles; it also provides a guide to identifying compatibility among donors and receptors of organs transplants.Objective: To establish HLA-A, HLA-B, and HLA.DRB1 allele, genotype and haplotype frequencies among patients treated at Clinica Colsanitas SA.Methods: 561 patients coming from different regions in Colombia, who were attended in 8 centers of the clinical laboratory of the Clinica Colsanitas in different cities of the country from January 2004 to August 2008, were included in this study. All were HLA-A,-B, and -DRB1 typified via SSP PCR. Allele, genotype and haplotype frequencies were estimated with STATA Software Version 9.0 and the GENEPOP genetic analysis package.Results: 19, 28, and 15 different alleles were identified for loci HLA-A,-B and -DRB1, respectively. Alleles found most frequently were A*24 (26.2%, A*02 (26%, B*35(22.7%, and DRB1*04 (24%. The most frequent genotypes were A*02,24 (14.2%, B*07,35 (5.5%, DRB1*01,04, and DRB1*04,04 (6.9%; while most the frequent haplotypes were HLA A*24, B*35 (9.2%, A*24, DRB1*04 (8.1%; B*35, DRB1*04 (7.8%, A*2 DRB1*04 (7.4%.Conclusion: The results obtained provide a useful reference framework for the population studied, allowing compatibility probability calculations to be performed for organ transplants.

  1. Neutrophil elastase enhances antigen presentation by upregulating human leukocyte antigen class I expression on tumor cells.

    Science.gov (United States)

    Chawla, Akhil; Alatrash, Gheath; Philips, Anne V; Qiao, Na; Sukhumalchandra, Pariya; Kerros, Celine; Diaconu, Iulia; Gall, Victor; Neal, Samantha; Peters, Haley L; Clise-Dwyer, Karen; Molldrem, Jeffrey J; Mittendorf, Elizabeth A

    2016-06-01

    Neutrophil elastase (NE) is an innate immune cell-derived inflammatory mediator that we have shown increases the presentation of tumor-associated peptide antigens in breast cancer. In this study, we extend these observations to show that NE uptake has a broad effect on enhancing antigen presentation by breast cancer cells. We show that NE increases human leukocyte antigen (HLA) class I expression on the surface of breast cancer cells in a concentration and time-dependent manner. HLA class I upregulation requires internalization of enzymatically active NE. Western blots of NE-treated breast cancer cells confirm that the expression of total HLA class I as well as the antigen-processing machinery proteins TAP1, LMP2, and calnexin does not change following NE treatment. This suggests that NE does not increase the efficiency of antigen processing; rather, it mediates the upregulation of HLA class I by stabilizing and reducing membrane recycling of HLA class I molecules. Furthermore, the effects of NE extend beyond breast cancer since the uptake of NE by EBV-LCL increases the presentation of HLA class I-restricted viral peptides, as shown by their increased sensitivity to lysis by EBV-specific CD8+ T cells. Together, our results show that NE uptake increases the responsiveness of breast cancer cells to adaptive immunity by broad upregulation of membrane HLA class I and support the conclusion that the innate inflammatory mediator NE enhances tumor cell recognition and increases tumor sensitivity to the host adaptive immune response. PMID:27129972

  2. A NOVel ELISPOT assay to quantify HLA-specific B cells in HLA-immunized individuals

    NARCIS (Netherlands)

    Heidt, S.; Roelen, D.L.; Vaal, Y.J. de; Kester, M.G.; Eijsink, C.; Thomas, S.; Besouw, N.M. van; Volk, H.D.; Weimar, W.; Claas, F.H.; Mulder, A.

    2012-01-01

    Quantification of the humoral alloimmune response is generally achieved by measuring serum HLA antibodies, which provides no information about the cells involved in the humoral immune response. Therefore, we have developed an HLA-specific B-cell ELISPOT assay allowing for quantification of B cells p

  3. HLA associations and HLA sharing in recurrent miscarriage : A systematic review and meta-analysis

    NARCIS (Netherlands)

    Meuleman, Tess; Lashley, Lisa E L O; Dekkers, Olaf M.; van Lith, Jan M M; Claas, Frans H J; Bloemenkamp, Kitty W M

    2015-01-01

    Problem: The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM). Method of study: A systematic literature search was performed for studies that evaluated the association between H

  4. Some Basic Aspects of HLA-G Biology

    Directory of Open Access Journals (Sweden)

    Estibaliz Alegre

    2014-01-01

    Full Text Available Human leukocyte antigen-G (HLA-G is a low polymorphic nonclassical HLA-I molecule restrictively expressed and with suppressive functions. HLA-G gene products are quite complex, with seven HLA-G isoforms, four membrane bound, and other three soluble isoforms that can suffer different posttranslational modifications or even complex formations. In addition, HLA-G has been described included in exosomes. In this review we will focus on HLA-G biochemistry with special emphasis to the mechanisms that regulate its expression and how the protein modifications affect the quantification in biological fluids.

  5. Heart conduction disturbance: an HLA-B27 associated disease.

    OpenAIRE

    Peeters, A J; ten Wolde, S; Sedney, M.I.; de Vries, R R; Dijkmans, B A

    1991-01-01

    In recent studies from Sweden an increased prevalence of HLA-B27 associated diseases and of HLA-B27 was found in an unselected group of men with permanently implanted pacemakers and with a heart block. Furthermore, a significantly increased prevalence of HLA-B27 was found in men with a pacemaker who had no clinical or radiological signs of HLA-B27 associated disease. To obtain more insight into the association between HLA-B27 and heart block, and the possible role of HLA-B27 in causing this b...

  6. Determination of HLA-B27 Subtypes in Iranian Patients with Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Mohamad Hossein Nicknam

    2008-03-01

    Full Text Available The human leukocyte antigen-B27 is one of the class I molecules of the major histocompatibility complex which is strongly associated with ankylosing spondylitis (AS. The strength of the disease association with B27 varies markedly among racial and ethnic populations. It is an allele family, which constitutes about 31 subtypes, with a considerable geographic and ethnic difference in distribution. It is important to know whether certain subtypes show any preferential association with AS. Because there is no report regarding HLA-B27 subtypes in Iranian patients with AS, the factthe main there are rarelystudies (if any; purpose of the present study was to assess the frequency of subtypes of human leukocyte antigen (HLA-B27 in patients with ankylosing spondylitis in Iranian populationOne hundred and nineteen AS patients (82 HLA-B27 positive and 37 HLA-B27 negative were selected for this study. HLA-B27 positive patients were selected screened for B*27 subtyping were performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP for B*27 subtyping.. The results of present study revealed that onlythat only two subtypes were detected in Iranian patients, including: B*2705 (52 patients, 63.4% and B*2702 (30 patients, 36.6%. Our results showed a restricted number of HLA-B27 subtypes associated with AS in Iran and an elevated frequency of the B*2705 allele in these patients similar to other Euro-Caucasoid (Aryan groups in the world.

  7. KIR : HLA association with clinical manifestations of HBV infection in Madurai, south India

    Indian Academy of Sciences (India)

    Narayanan Kalyanaraman; Lakshmikanthan Thayumanavan; Mariakuttikan Jayalakshmi

    2016-03-01

    The antiviral action of natural killer (NK) cells is regulated by a wide repertoire of germ-line encoded membrane receptors which recognize the expression of certain self-molecules on target cells. Among the receptors, killer cell immunoglobulinlikereceptor (KIR) which recognizes the expression of human leukocyte antigen (HLA) class I has a predominant role in regulating the effector functions of NK cells, particularly in viral infections. We studied a total of 128 hepatitis B virus (HBV)patients (15 acute, 43 asymptomatic, 27 chronic and 43 with other liver diseases) while attending the Department of Medical Gastroenterology, Government Rajaji Hospital, Madurai, India, and 128 ethnic matched control to find the association between the KIR : HLA genes and differential manifestations of HBV. KIR and its ligand HLA polymorphism were identified by DNAPCR methods. The activatory receptor KIR-2DS1 was significantly elevated in various disease categories, namely asymptomatic, chronic and other HBV, except acute HBV infection. Whereas, KIR 2DS3 in acute and chronic patients and KIR 2DS5 and 3DS1 in asymptomatic individuals. Among various KIR–HLA combinations, homozygous 2DS2:C1 and individuals with 3DSI:BW4 (OR = 3.23, CI = 1.55–6.7, Pc = 0.02) are associated with HBV asymptomatism, while most of the two domain inhibitory receptors with their ligands showed significant risk in other liver diseases. Further, KIR3DL1 : HLA Bw4Iso80 (OR = 3.89, 95% CI = 1.58–9.55, Pc = 0.004) is related with higher risk for asymptomatic infection when compared with chronic HBV. Thus, the select KIR : HLA alleles and combinations seem to direct the NK cell activities and immune response in different directions resulting in varied symptoms and manifestations in the subgroups of HBV-infected patientsstudied.

  8. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

    OpenAIRE

    Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; ICHINOKAWA, MASAOMI; KUBOTA, KANAKO C.; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; DOSAKA-AKITA, HIROTOSHI; Matsuno, Yoshihiro; Kondo, Satoshi

    2012-01-01

    The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohi...

  9. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

    OpenAIRE

    Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; ICHINOKAWA, MASAOMI; KUBOTA, KANAKO C.; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; DOSAKA-AKITA, HIROTOSHI; Matsuno, Yoshihiro; Kondo, Satoshi

    2011-01-01

    The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohi...

  10. Povezanost mikrosatelita HLA i gena HLA-B*27 u bolesnika s psorijatičnim artritisom u hrvatskoj populaciji

    OpenAIRE

    Štimac, Davor; Grubić, Zorana; Štingl, Katarina; Perić, Porin; Ćurković, Božidar; Žunec, Renata

    2011-01-01

    Istraživana je raznovrsnost četiri mikrosatelita HLA (D6S248, D6S2674, D6S2811 i D6S273) u skupini bolesnika s psorijatičnim artritisom (PsA) (N=22) i zdravim osobama (K; N=94) pozitivnima za gen HLA-B*27, te povezanost haplotipskih veza gena HLA-B*27 s PsA. Svi ispitanici bili su prethodno tipizirani za gene HLA-A i -B metodom PCR-SSP i bili su HLA-B*27 pozitivni. Mikrosateliti HLA su analizirani metodom PCR-STR i elektroforezom u ALFexpress sekvenceru. Analiza raspodjele alela mikrosatelita...

  11. MULTIPRED2: a computational system for large-scale identification of peptides predicted to bind to HLA supertypes and alleles.

    Science.gov (United States)

    Zhang, Guang Lan; DeLuca, David S; Keskin, Derin B; Chitkushev, Lou; Zlateva, Tanya; Lund, Ole; Reinherz, Ellis L; Brusic, Vladimir

    2011-11-30

    MULTIPRED2 is a computational system for facile prediction of peptide binding to multiple alleles belonging to human leukocyte antigen (HLA) class I and class II DR molecules. It enables prediction of peptide binding to products of individual HLA alleles, combination of alleles, or HLA supertypes. NetMHCpan and NetMHCIIpan are used as prediction engines. The 13 HLA Class I supertypes are A1, A2, A3, A24, B7, B8, B27, B44, B58, B62, C1, and C4. The 13 HLA Class II DR supertypes are DR1, DR3, DR4, DR6, DR7, DR8, DR9, DR11, DR12, DR13, DR14, DR15, and DR16. In total, MULTIPRED2 enables prediction of peptide binding to 1077 variants representing 26 HLA supertypes. MULTIPRED2 has visualization modules for mapping promiscuous T-cell epitopes as well as those regions of high target concentration - referred to as T-cell epitope hotspots. Novel graphic representations are employed to display the predicted binding peptides and immunological hotspots in an intuitive manner and also to provide a global view of results as heat maps. Another function of MULTIPRED2, which has direct relevance to vaccine design, is the calculation of population coverage. Currently it calculates population coverage in five major groups in North America. MULTIPRED2 is an important tool to complement wet-lab experimental methods for identification of T-cell epitopes. It is available at http://cvc.dfci.harvard.edu/multipred2/. PMID:21130094

  12. 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

    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...

  13. Epistatic interaction of ERAP1 and HLA-B in Behcet disease: a replication study in the Spanish population.

    Directory of Open Access Journals (Sweden)

    Marta Conde-Jaldón

    Full Text Available Behçet's disease (BD is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078 and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987 associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.

  14. HLA genotypes in Turkish patients with myasthenia gravis: comparison with multiple sclerosis patients on the basis of clinical subtypes and demographic features.

    Science.gov (United States)

    Dönmez, Berril; Ozakbas, Serkan; Oktem, Mehmet Ali; Gedizlioglu, Muhtesem; Coker, Isil; Genc, Ahmet; Idiman, Egemen

    2004-07-01

    The nature and intensity of the association of myasthenia gravis (MG) with distinct human leukocyte antigens (HLA) haplotypes differ between ethnic populations. The aims of the present study were to examine the relationship between HLA class I and II haplotypes and MG; to show the HLA associations with various MG subsets; and to investigate the association between MG and clinical subgroups of multiple sclerosis (MS) regarding HLA haplotypes. A total of 66 patients with MG were enrolled onto the study. The mean age at onset was 42.01 years. A total of 122 clinically definite MS patients and 188 healthy subjects were examined as control groups. The present study clearly showed associations with HLA-DR3, -B8, -A1, and -A2 in MG. In patients with early-onset MG, associations with HLA-DR3, -B8, and -A2 were stronger. When compared with MS, in the MG group, there was still a strong association with -B8, -DR3, and -A1. In subgroup analysis, there was no difference between MG and primary progressive MS patients. On the basis of the presence of anti-AChR antibodies, there was a statistically significant association with HLA-DR3. On the basis of presence of thymoma, no HLA allele showed clear associations in MG patients with thymoma. This is the first study to examine the relationship between HLA haplotypes and MG in the Turkish population and to compare MG with another autoimmune disease, MS, on the basis of the HLA haplotypes. Further investigations with a larger population are required to explain this finding. PMID:15301866

  15. Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris.

    OpenAIRE

    Ahmed, A. R.; Wagner, R; Khatri, K; Notani, G.; Awdeh, Z; Alper, C A; Yunis, E J

    1991-01-01

    Previous studies demonstrated that HLA-DR4 was markedly increased among Ashkenazi Jewish patients with pemphigus vulgaris (PV), almost entirely as the common Jewish extended haplotype [HLA-B38, SC21, DR4, DQw8] or as the haplotype HLA-B35, SC31, DR4, DQw8, and that HLA-DR4, DQw8 was distributed among patients in a manner consistent with dominant expression of a class II (D-region or D-region-linked) susceptibility gene. In the present study of major histocompatibility complex (MHC) haplotypes...

  16. Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3.

    Science.gov (United States)

    Price, P; Santoso, L; Mastaglia, F; Garlepp, M; Kok, C C; Allcock, R; Laing, N

    2004-11-01

    Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the association with HLA-DR3 and other genes in the central MHC and class II region was further investigated in a group of 42 sIBM patients and in an ethnically similar control group (n = 214), using single-nucleotide polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients. Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region and is expressed in muscle. Carriage of allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently or share a critical allele. PMID:15496200

  17. HLA-B51 and haplotypic diversity of B-Cw associations: implications for matching in unrelated hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bettens, F; Nicoloso de Faveri, G; Tiercy, J-M

    2009-04-01

    In unrelated hematopoietic stem cell transplantation (HSCT), human leukocyte antigen (HLA)-C locus incompatibilities occur frequently and are associated with increased risk of posttransplant complications. Because HLA-B51 is associated with a high rate of Cw disparities, we performed a comprehensive four-digit typing analysis of 140 ABCDRB1 B51 genotypes proven by pedigree analysis and 311 unrelated donors selected for 75 B51-positive patients. In addition, 145 A1/Ax-B8/B51-DR3/DRx donors were HLA typed at a high-resolution level and tested for three microsatellite (Msat) polymorphisms located in the HLA class I and III regions. Based on these data sets, 182 different ABCDR haplotypes with 14 different B-Cw associations were detected. Rates of Cw mismatches were shown to be highly correlated with the ABDRB1 haplotypes. We have computed 21 B51 haplotypes that disclose a high probability of HLA-C allele matching and 30 haplotypes with a low (HLA-C allele frequency profiles were quite different in these two groups, with a more heterogeneous distribution in the low matching probability group. HLA-Cw*1502 was inversely correlated with the likelihood to identify a Cw-mismatched donor: it was present in 61% of the high vs 18% of the low probability group (P A1-B8-DR3 haplotype. HLA-B51 haplotypes therefore exhibit a high diversity at the level of B-Cw associations and of non-HLA polymorphisms in the class I and III regions. Such heterogeneity negatively impacts on overall matching in HSCT. PMID:19317740

  18. High resolution human leukocyte antigen class I allele frequencies and HIV-1 infection associations in Chinese Han and Uyghur cohorts.

    Directory of Open Access Journals (Sweden)

    Yanhou Liu

    Full Text Available BACKGROUND: Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort. METHODOLOGY/PRINCIPAL FINDINGS: Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group. CONCLUSIONS: At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the

  19. Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis.

    Science.gov (United States)

    Okada, Yukinori; Suzuki, Akari; Ikari, Katsunori; Terao, Chikashi; Kochi, Yuta; Ohmura, Koichiro; Higasa, Koichiro; Akiyama, Masato; Ashikawa, Kyota; Kanai, Masahiro; Hirata, Jun; Suita, Naomasa; Teo, Yik-Ying; Xu, Huji; Bae, Sang-Cheol; Takahashi, Atsushi; Momozawa, Yukihide; Matsuda, Koichi; Momohara, Shigeki; Taniguchi, Atsuo; Yamada, Ryo; Mimori, Tsuneyo; Kubo, Michiaki; Brown, Matthew A; Raychaudhuri, Soumya; Matsuda, Fumihiko; Yamanaka, Hisashi; Kamatani, Yoichiro; Yamamoto, Kazuhiko

    2016-08-01

    Despite the progress in human leukocyte antigen (HLA) causal variant mapping, independent localization of major histocompatibility complex (MHC) risk from classical HLA genes is challenging. Here, we conducted a large-scale MHC fine-mapping analysis of rheumatoid arthritis (RA) in a Japanese population (6,244 RA cases and 23,731 controls) population by using HLA imputation, followed by a multi-ethnic validation study including east Asian and European populations (n = 7,097 and 23,149, respectively). Our study identified an independent risk of a synonymous mutation at HLA-DOA, a non-classical HLA gene, on anti-citrullinated protein autoantibody (ACPA)-positive RA risk (p = 1.4 × 10(-9)), which demonstrated a cis-expression quantitative trait loci (cis-eQTL) effect on HLA-DOA expression. Trans-ethnic comparison revealed different linkage disequilibrium (LD) patterns in HLA-DOA and HLA-DRB1, explaining the observed HLA-DOA variant risk heterogeneity among ethnicities, which was most evident in the Japanese population. Although previous HLA fine-mapping studies have identified amino acid polymorphisms of the classical HLA genes as driving genetic susceptibility to disease, our study additionally identifies the dosage contribution of a non-classical HLA gene to disease etiology. Our study contributes to the understanding of HLA immunology in human diseases and suggests the value of incorporating additional ancestry in MHC fine-mapping. PMID:27486778

  20. Design and Validation of Conditional Ligands for HLA-B*08:01, HLA-B*15:01, HLA-B*35:01, and HLA-B*44:05

    DEFF Research Database (Denmark)

    Frøsig, Thomas Mørch; Yap, Jiawei; Seremet, Tina;

    2015-01-01

    We designed conditional ligands restricted to HLA-B*08:01, 2B*35:01, and 2B*44:05 and proved the use of a conditional ligand previously designed for HLA-B*15:02 together with HLA-B*15:01. Furthermore, we compared the detection capabilities of specific HLA-B*15:01-restricted T cells using the HLA......-B*15:01 and HLA-B*15:02 major histocompatibility complex (MHC) multimers and found remarkable differences in the staining patterns detected by flow cytometry. These new conditional ligands greatly add to the application of MHC-based technologies in the analyses of T-cell recognition as they represent...... frequently expressed HLA-B molecules. This expansion of conditional ligands is important to allow T-cell detection over a wide range of HLA restrictions, and provide comprehensive understanding of the T-cell recognition in a given context....

  1. Absent in Melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers.

    Science.gov (United States)

    Lee, J; Li, L; Gretz, N; Gebert, J; Dihlmann, S

    2012-03-01

    Absent in Melanoma 2 (AIM2) is a member of the HIN-200 family of hematopoietic, IFN-inducible, nuclear proteins, associated with both, infection defense and tumor pathology. Recently, AIM2 was found to act as a DNA sensor in innate immunity. In addition, we and others have previously demonstrated a high frequency of AIM2-alterations in microsatellite unstable (MSI-H) tumors. To further elucidate AIM2 function in colorectal tumors, we here addressed AIM2-responsive target genes by microarray based gene expression profiling of 22 244 human genes. A total of 111 transcripts were significantly upregulated, whereas 80 transcripts turned out to be significantly downregulated in HCT116 cells, constitutively expressing AIM2, compared with AIM2-negative cells. Among the upregulated genes that were validated by quantitative PCR and western blotting we recognized several interferon-stimulated genes (ISGs: IFIT1, IFIT2, IFIT3, IFI6, IRF7, ISG15, HLA-DRA, HLA-DRB, TLR3 and CIITA), as well as genes involved in intercellular adhesion and matrix remodeling. Expression of ISGs correlated with expression of AIM2 in 10 different IFN-γ treated colorectal cancer cell lines. Moreover, small interfering RNA-mediated knock-down of AIM2 resulted in reduced expression of HLA-DRA, HLA-DRB and CIITA in IFN-γ-treated cells. IFN-γ independent induction of HLA-DR genes and their encoded proteins was also demonstrated upon doxycyclin-regulated transient induction of AIM2. Luciferase reporter assays revealed induction of the HLA-DR promoter upon AIM2 transfection in different cell lines. STAT-signaling was not involved in IFN-γ independent induction of ISGs, arguing against participation of cytokines released in an autostimulating manner. Our data indicate that AIM2 mediates both IFN-γ dependent and independent induction of several ISGs, including genes encoding the major histocompatibility complex (MHC) class II antigens HLA-DR-α and -β. This suggests a novel role of the IFN/AIM2/ISG

  2. Lysis of pig endothelium by IL-2 activated human natural killer cells is inhibited by swine and human major histocompatibility complex (MHC) class I gene products.

    Science.gov (United States)

    Itescu, S; Artrip, J H; Kwiatkowski, P A; Wang, S F; Minanov, O P; Morgenthau, A S; Michler, R E

    1997-01-01

    We have previously described a form of xenograft rejection, mediated by natural killer (NK) cells, occurring in pig-to-primate organ transplants beyond the period of antibody-mediated hyperacute rejection. In this study, two distinct NK activation pathways were identified as mechanisms of pig aortic endotheliual cell (PAEC) lysis by human NK cells. Using an antibody-dependent cellular cytotoxicity (ADCC) assay, a progressive increase in human NK lysis of PAEC was observed following incubation with human IgG at increasing serum titer. In the absence of IgG, a second mechanism of PAEC lysis by human NK cells was observed following activation with IL-2. IL-2 activation of human NK cells increased lysis of PAEC by over 3-fold compared with ADCC. These results indicate that IL-2 activation of human NK cells induces significantly higher levels of lytic activity than does conventional ADCC involving IgG and FcRIII. We next investigated the role of MHC class I molecules in the regulation of NK lysis following IL-2 activation. PAEC expression of SLA class I molecules was increased by up to 75% by treatment with human TNFa. Following treatment with TNFa at 1 u/ml, IL-2 activated human NK lysis of PAEC was inhibited at every effector:target (E:T) ratio tested. Maximal effect occurred at an E:T ratio of 10:1, with TNFa inhibiting specific lysis by 59% (p < 0.01). Incubation with an anti-SLA class I Mab, but not IgG isotype control, abrogated the protective effects of TNFa on NK lysis of PAEC, suggesting direct inhibitory effects of SLA class I molecules on human NK function. To investigate whether human MHC class I molecules might have similar effects on human NK lysis of PAEC, further experiments were performed using a soluble peptide derived from the alpha-helical region of HLA-B7. Incubation with the HLA-B7 derived peptide significantly reduced the IL-2 activated NK lytic activity against PAEC in a dose-dependent fashion. Maximal effect occurred at a concentration of 10 mg

  3. A web resource for mining HLA associations with adverse drug reactions: HLA-ADR.

    Science.gov (United States)

    Ghattaoraya, Gurpreet S; Dundar, Yenal; González-Galarza, Faviel F; Maia, Maria Helena Thomaz; Santos, Eduardo José Melo; da Silva, Andréa Luciana Soares; McCabe, Antony; Middleton, Derek; Alfirevic, Ana; Dickson, Rumona; Jones, Andrew R

    2016-01-01

    Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/. PMID:27189608

  4. HLA-G DNA sequence variants and risk of perinatal HIV-1 transmission

    Directory of Open Access Journals (Sweden)

    Shamsa Falah

    2006-10-01

    Full Text Available Abstract Background HLA-G gene is a non-classical MHC class 1 molecule that is highly expressed in the trophoblast at the maternal-fetal interface. In an attempt to elucidate possible immunological mechanisms facilitating protection of infants born to human immunodeficiency virus type (HIV-1 infected mothers, we have been studying genetic variations in the coding and untranslated regions of HLA-G antigen between HIV-1-infected mothers and their infected or uninfected infants. This study investigated whether HLA-G DNA sequence variants are associated with perinatal HIV-1 transmission. Results Genomic DNA samples were obtained from a nested case-control study of 34 mother-child pairs co-enrolled in a cohort of the Perinatal AIDS Collaborative Transmission Study in New York. The samples were from two groups predominantly of African-American and Hispanic origin: In the first group, both mother and child were HIV-1-infected; in the second group, only the mother was infected while the child remained uninfected. Genotyping of HLA-G gene were performed on the extracted DNA from peripheral blood mononuclear cells using PCR based sequencing and restriction fragment-length polymorphism analyses. Among the studied HLA-G exons, dissimilarities in HLA-G DNA sequence variants between the HIV-1 non-transmitting mother child pairs were mostly observed in exon 8-3'-untranslated region at nucleotide positions T3742A, C3743T, G3777C (P = 0.001. Non-transmitting HIV-1 mother child pairs exhibited dissimilarities at nucleotide position C3743T allele with decreased risk of perinatal HIV-1 transmission, compared with HIV-1 transmitting mother-child pairs carrying this allele (odds ratio 0.02 [95% confidence interval 0.00–0.15] P = 0.00001. In addition, heterozygous dissimilarities at nucleotide positions C634G and 714 insT/G in the 5'-upstream regulatory region were observed between the mother child pairs of the HIV-1-non-transmitting group while homozygous

  5. sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion.

    Science.gov (United States)

    Zidi, Inès; Rizzo, Roberta; Bouaziz, Aicha; Laaribi, Ahmed Baligh; Zidi, Nour; Di Luca, Dario; Tlili, Henda; Bortolotti, Daria

    2016-04-01

    Pregnancy is associated with increased levels of soluble (s) human leukocyte antigen (HLA)-G molecules, while during abortion these molecules are decreased. To date, little is known about the role of sHLA-G isoforms during abortion. In this study, we investigated the levels of total sHLA-G and its isoforms: HLA-G1 (membrane shedded isoform) and alternative spliced HLA-G5 in plasma samples obtained from 55 women who had experienced spontaneous abortion, 108 pregnant healthy women and 56 non pregnant healthy women. We found that pregnant women exhibited higher amounts of sHLA-G compared to either non pregnant women or women with abortion. Among women who had experienced spontaneous abortion, women with recurrent abortions (RSA) had lower sHLA-G than women with only one abortion. In particular, RSA women were characterized by the absence of sHLA-G1 isoform, suggesting a possible implication in abortion event. PMID:26812178

  6. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  7. Real-time Scheduling of HLA Simulator Components

    NARCIS (Netherlands)

    Jansen, R.E.J.; Huiskamp, W.; Boomgaardt, J.J.; Brasse, M.

    2004-01-01

    For several years TNO has done research on the use of component based HLA federates. An individual simulator, participating in an HLA federation, can itself be composed of various components interacting through the same HLA interface as the overall federation. Simulator components communicate via a

  8. HLA-DP specific responses in allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Rutten, Caroline Elisabeth

    2013-01-01

    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated

  9. Effect of HLA-A, B genotype on the content of soluble HLA classⅠantigen%HLA-A,B基因型别对可溶性HLA Ⅰ类抗原含量的影响

    Institute of Scientific and Technical Information of China (English)

    倪宏英; 陈长荣; 裴斌

    2005-01-01

    目的了解HLA-A,B基因型别对可溶性HLA Ⅰ类抗原含量的影响.方法 HLA-A,B基因型别用反相PCR-SSO技术检测,可溶性HLA I类抗原的含量用夹心ELISA方法测定.结果在福建省汉族人群中基因型别为HLA-A*24的个体,可溶性HLA Ⅰ类抗原的含量显著高于平均水平;HLA-A*2和A*33基因的携带者可溶性HLA Ⅰ类抗原的含量显著低于平均水平;HLA-A*11、B*15、B*40和B*58的个体可溶性HLA Ⅰ类抗原的含量与平均水平比较无显著差异.结论 HLA-A基因型别的不同可能造成可溶性HLA Ⅰ类抗原含量的差异.

  10. HLA-B27 Expression Does Not Modulate Intracellular Chlamydia trachomatis Infection of Cell Lines

    OpenAIRE

    Young, J. L.; Smith, L; Matyszak, M. K.; Gaston, J S H

    2001-01-01

    Chlamydia trachomatis is an obligate intracellular pathogen. Infection of susceptible individuals with this bacterium can trigger the development of reactive arthritis, an acute inflammation that is associated with the expression of the class I major histocompatibility antigen, HLA-B27. Other facultative intracellular pathogens, such as Yersinia and Salmonella spp., are also known triggers of reactive arthritis. Previous studies report conflicting results concerning whether the presence of HL...

  11. Languages, geography and HLA haplotypes in native American and Asian populations.

    OpenAIRE

    Monsalve, M V; Helgason, A; Devine, D V

    1999-01-01

    A number of studies based on linguistic, dental and genetic data have proposed that the colonization of the New World took place in three separate waves of migration from North-East Asia. Recently, other studies have suggested that only one major migration occurred. It is the aim of this study to assess these opposing migration hypotheses using molecular-typed HLA class II alleles to compare the relationships between linguistic and genetic data in contemporary Native American populations. Our...

  12. The Pharmacogenomic HLA Biomarker Associated to Adverse Abacavir Reactions: Comparative Analysis of Different Genotyping Methods

    OpenAIRE

    Zampatti, Stefania; Novelli, Giuseppe; Cascella, Raffaella; Giardina, Emiliano; Stocchi, Laura; Pirazzoli, Antonella

    2012-01-01

    Many pharmacogenomic biomarkers (PGBM) were identified and translated into clinical practice, affecting the usage of drugs via label updates. In this context, abacavir is one of the most brilliant examples of pharmacogenetic studies translated into clinical practice. Pharmacogenetic studies have revealed that abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to...

  13. Human leukocyte antigen-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies

    NARCIS (Netherlands)

    Kremer, A.N.; Meijden, E.D. van der; Honders, M.W.; Pont, M.J.; Goeman, J.J.; Falkenburg, J.H.F.; Griffioen, M.

    2014-01-01

    Hematological malignancies often express surface HLA class II, making them attractive targets for CD4+ T cell therapy. We previously demonstrated that HLA class II ligands can be divided into DM-resistant and DM-sensitive antigens. In contrast to presentation of DM-resistant antigens, presentation o

  14. The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes.

    Science.gov (United States)

    Silva, H P V; Ururahy, M A G; Souza, K S C; Loureiro, M B; Oliveira, Y M C; Oliveira, G H M; Luchessi, A D; Carvalho, K T C; Freitas, J C O C; Donadi, E A; Hirata, R D C; Almeida, M G; Arrais, R F; Hirata, M H; Rezende, A A

    2016-01-01

    Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility. PMID:26492519

  15. HLA-G in human early pregnancy: control of uterine immune cell activation and likely vascular remodeling.

    Science.gov (United States)

    Le Bouteiller, Philippe

    2015-01-01

    Despite a number of controversies, the functional importance of human leukocyte antigen G (HLA-G) in early human pregnancy is now sustained by a large amount of sound data. Membrane-bound and soluble HLA-G isoforms, either as β2-microglobulin-free or -associated as monomers or dimers, are expressed by different trophoblast subpopulations, the only fetal-derived cells that are directly in contact with maternal cells (maternal-fetal interfaces). Trophoblast HLA-G is the specific ligand of multiple cellular receptors present in maternal immune and non-immune cells, including CD8, leukocyte immunoglobulin-like receptor (LILR) B1, LILRB2, killer cell immunoglobulin-like receptor (KIR) 2DL4, and possibly CD160. Trophoblast HLA-G specific engagement of these cellular receptors triggers either inhibitory or activating signals in decidual CD8 + T cells, CD4 + T cells, natural killer (NK) cells, macrophages, dendritic cells, or endothelial cells. Such HLA-G-receptor specific interactions first contribute to limit potentially harmful maternal anti-paternal immune response by impairment of decidual NK cell cytotoxicity, inhibition of CD4 + and CD8 + T-cell and B-cell proliferation, and induction of apoptosis of activated CD8 + T cells. Second, these HLA-G specific interactions contribute to stimulate placental development through secretion of angiogenic factors by decidual NK cells and macrophages, and to provide a protective effect for the outcome of pregnancy by the secretion of interleukin (IL)-4 by decidual trophoblast antigen-specific CD4 + T cells. PMID:25163504

  16. Clinical characteristics and HLA alleles of a family with simultaneously occurring alopecia areata.

    Science.gov (United States)

    Emre, Selma; Metin, Ahmet; Caykoylu, Ali; Akoglu, Gulsen; Ceylan, Gülay G; Oztekin, Aynure; Col, Esra S

    2016-06-01

    Alopecia areata (AA) is a T-cell-mediated autoimmune disease resulting in partial or total noncicatricial hair loss. HLA class II antigens are the most important markers that constitute genetic predisposition to AA. Various life events and intense psychological stress may play an important role in triggering AA attacks. We report an unusual case series of 4 family members who had simultaneously occurring active AA lesions. Our aim was to evaluate the clinical and psychiatric features of 4 cases of active AA lesions occurring simultaneously in a family and determine HLA alleles. The clinical and psychological features of all patients were examined. HLA antigen DNA typing was performed by polymerase chain reaction with sequence-specific primers. All patients had typical AA lesions over the scalp and/or beard area. Psychological examinations revealed obsessive-compulsive personality disorder in the proband's parents as well as anxiety and lack of self-confidence in both the proband and his sister. HLA antigen types were not commonly shared with family members. These findings suggest that AA presenting concurrently in members of the same family was not associated with genetic predisposition. Shared psychological disorders and stressful life events might be the major key points in the concurrent presentation of these familial AA cases and development of resistance against treatments. PMID:27416096

  17. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.

    Science.gov (United States)

    Salerno-Gonçalves, Rosângela; Fernandez-Viña, Marcelo; Lewinsohn, David M; Sztein, Marcelo B

    2004-11-01

    Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net frequency of IFN-gamma spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections. PMID:15494539

  18. Integrating in silico and in vitro analysis of peptide binding affinity to HLA-Cw*0102: a bioinformatic approach to the prediction of new epitopes.

    Directory of Open Access Journals (Sweden)

    Valerie A Walshe

    Full Text Available BACKGROUND: Predictive models of peptide-Major Histocompatibility Complex (MHC binding affinity are important components of modern computational immunovaccinology. Here, we describe the development and deployment of a reliable peptide-binding prediction method for a previously poorly-characterized human MHC class I allele, HLA-Cw*0102. METHODOLOGY/FINDINGS: Using an in-house, flow cytometry-based MHC stabilization assay we generated novel peptide binding data, from which we derived a precise two-dimensional quantitative structure-activity relationship (2D-QSAR binding model. This allowed us to explore the peptide specificity of HLA-Cw*0102 molecule in detail. We used this model to design peptides optimized for HLA-Cw*0102-binding. Experimental analysis showed these peptides to have high binding affinities for the HLA-Cw*0102 molecule. As a functional validation of our approach, we also predicted HLA-Cw*0102-binding peptides within the HIV-1 genome, identifying a set of potent binding peptides. The most affine of these binding peptides was subsequently determined to be an epitope recognized in a subset of HLA-Cw*0102-positive individuals chronically infected with HIV-1. CONCLUSIONS/SIGNIFICANCE: A functionally-validated in silico-in vitro approach to the reliable and efficient prediction of peptide binding to a previously uncharacterized human MHC allele HLA-Cw*0102 was developed. This technique is generally applicable to all T cell epitope identification problems in immunology and vaccinology.

  19. Influence of HLA-DRB1 and HLA-DQB1 alleles on IgG antibody response to the P. vivax MSP-1, MSP-3α and MSP-9 in individuals from Brazilian endemic area.

    Directory of Open Access Journals (Sweden)

    Josué C Lima-Junior

    Full Text Available BACKGROUND: The antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials. METHODS AND FINDINGS: In this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276 against P. vivax Merozoite Surface Protein-1 (MSP-1, MSP-3α and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%, PvMSP-3 (77% and PvMSP-9 (76%. Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1*01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein. CONCLUSIONS: HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.

  20. HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    Full Text Available BACKGROUND: Despite the extensive genetic diversity of HIV-1, viral evolution in response to immune selective pressures follows broadly predictable mutational patterns. Sites and pathways of Human Leukocyte-Antigen (HLA-associated polymorphisms in HIV-1 have been identified through the analysis of population-level data, but the full extent of immune escape pathways remains incompletely characterized. Here, in the largest analysis of HIV-1 subtype B sequences undertaken to date, we identify HLA-associated polymorphisms in the three HIV-1 proteins most commonly considered in cellular-based vaccine strategies. Results are organized into protein-wide escape maps illustrating the sites and pathways of HLA-driven viral evolution. METHODOLOGY/PRINCIPAL FINDINGS: HLA-associated polymorphisms were identified in HIV-1 Gag, Pol and Nef in a multicenter cohort of >1500 chronically subtype-B infected, treatment-naïve individuals from established cohorts in Canada, the USA and Western Australia. At q< or =0.05, 282 codons commonly mutating under HLA-associated immune pressures were identified in these three proteins. The greatest density of associations was observed in Nef (where close to 40% of codons exhibited a significant HLA association, followed by Gag then Pol (where approximately 15-20% of codons exhibited HLA associations, confirming the extensive impact of immune selection on HIV evolution and diversity. Analysis of HIV codon covariation patterns identified over 2000 codon-codon interactions at q< or =0.05, illustrating the dense and complex networks of linked escape and secondary/compensatory mutations. CONCLUSIONS/SIGNIFICANCE: The immune escape maps and associated data are intended to serve as a user-friendly guide to the locations of common escape mutations and covarying codons in HIV-1 subtype B, and as a resource facilitating the systematic identification and classification of immune escape mutations. These resources should facilitate

  1. Distribution of HLA-DRB1 and HLA-DQB1 alleles in Lak population of Iran.

    Science.gov (United States)

    Varzi, Ali Mohammad; Shahsavar, Farhad; Tarrahi, Mohammad Javad

    2016-07-01

    Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and encode the highly polymorphic molecules critically involved in immune responses. Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine the HLA-DRB1 and HLA-DQB1 allele frequencies in 100 unrelated Lak individuals from Lorestan province of Iran. Finally, we compared the results with those previously described in four other Iranian populations. Commercial HLA-Type kits were used for determination of the HLA-DRB1 and HLA-DQB1 allele frequencies. Differences between populations in the distribution of HLA-DRB1 and HLA-DQB1 alleles were estimated by χ2 test with Yate's correction and Fisher's exact test. The most frequent HLA-DRB1 alleles were (*)1103=4 (23%), (*)1502 (9.5%), (*)0701 (9%), (*)0301 (8.5%), (*)1101 (7.5%) and (*)1501 (6%) while HLA-DQB1(*)0301 (40%), (*)0201 (15%), (*)0502 (10.5%), (*)0303 (10%), (*)0602=3 (9.5%), and (*)0501 (7.5%) were the most frequent alleles in Lak population. HLA-DRB1(*)0409, (*)0804, (*)1102, (*)1112, (*)1405, and HLA-DQB1(*)0503, (*)0604 were the least observed frequencies in Lak population. Our results based on HLA-DRB1 and HLA-DQB1 allele frequencies showed that the Lak population possesses the previously reported general features of the Lur and Kurd populations but still with unique, decreased or increased frequencies of several alleles. In other words, the Lak population is close to Lurs Khorramabadi and Kurd but far from Lurs Kohkiloyeh/Boyerahmad and Bakhtiari. PMID:27189628

  2. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

    OpenAIRE

    Romanos, Jihane; Rosen, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C.; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; Van Heel, David A.; Cukrowska, Bozena; Bruno, Valentina

    2014-01-01

    Background The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective We explored whether CD risk prediction can be improved by adding non-HLA-susceptible varian...

  3. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

    OpenAIRE

    Romanos, Jihane; Rosén, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C.; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; Van Heel, David A.; Cukrowska, Bozena; Bruno, Valentina

    2014-01-01

    Background: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible vari...

  4. Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

    Science.gov (United States)

    Bronke, Corine; Palmer, Nanette M; Westerlaken, Geertje H A; Toebes, Mireille; van Schijndel, Gijs M W; Purwaha, Veenu; van Meijgaarden, Krista E; Schumacher, Ton N M; van Baarle, Debbie; Tesselaar, Kiki; Geluk, Annemieke

    2005-09-01

    In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.84% of CD4+ T cells by intracellular cytokine staining. In peripheral blood mononuclear cells from M. tuberculosis-exposed, Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated, or CMV-seropositive individuals, we were able to directly detect with both tetramers epitope-specific T cells up to 0.62% and 0.45% of the CD4+ T-cell population reactive to M. tuberculosis and CMV, respectively. After a 6-day culture with peptide p510-522, the frequency of CMV-specific tetramer-binding T cells was expanded up to 9.90% tetramer+ CFSElow (5,6-carboxyfluorescein diacetate succinimidyl ester) cells within the CD4+ T-cell population, further confirming the specificity of the tetrameric molecules. Thus, HLA-DR3/peptide tetrameric molecules can be used to investigate HLA-DR3-restricted antigen-specific CD4+ T cells in clinical disease or after vaccination. PMID:16360834

  5. HLA-DR expression and disease activity in ulcerative colitis

    DEFF Research Database (Denmark)

    Poulsen, L O; Elling, P; Sørensen, Flemming Brandt;

    1986-01-01

    In 12 patients with active ulcerative colitis (UC) the rectal epithelial cells were analyzed for HLA-DR antigens by an immunohistochemical technique. The clinical, rectoscopic, and histologic stages were also determined. The investigations were carried out at the beginning of the study and 2 weeks...... and 3 months later. The rectal epithelial cells were HLA-DR-positive in all patients at the first two examinations. After 3 months five patients had changed to an HLA-DR-negative stage, whereas the other seven patients remained HLA-DR-positive. Closer analyses showed that expression/nonexpression of...... HLA-DR antigens on rectal epithelial cells of patients with UC could not be predicted from the clinical, rectoscopic, or histologic findings. HLA-DR expression is normally restricted to immunocompetent cells. The presence of HLA-DR antigens on epithelial cells may be a consequence of immunological...

  6. Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles

    DEFF Research Database (Denmark)

    Mothé, Bianca R.; Southwood, Scott; Sidney, John;

    2013-01-01

    deciphering outcomes of infection and vaccine efficacy. In this study, we have provided detailed characterization of six prevalent Chinese rhesus macaque MHC class I alleles, yielding a combined phenotypic frequency of 29 %. The peptide-binding specificity of two of these alleles, Mamu-A2*01:02 and Mamu-B*010......:01, as well as the previously characterized allele Mamu-B*003:01 (and Indian rhesus Mamu-B*003:01), was found to be analogous to that of alleles in the HLA-B27 supertype family. Specific alleles in the HLA-B27 supertype family, including HLA-B*27:05, have been associated with long-term nonprogression to...... AIDS in humans. All six alleles characterized in the present study were found to have specificities analogous to HLA supertype alleles. These data contribute to the concept that Chinese rhesus macaque MHC immunogenetics is more similar to HLA than their Indian rhesus macaque counterparts and thereby...

  7. Saliva soluble HLA as a potential marker of response to interferon-β1a in multiple sclerosis: A preliminary study

    Directory of Open Access Journals (Sweden)

    McLarty Jerry

    2007-07-01

    Full Text Available Abstract Objective Potential surrogate markers of disease activity, including response to therapy, are particularly important in a neurological disorder such as multiple sclerosis (MS which often has a fluctuating course. Based upon previous studies in our laboratory, we hypothesized that measurement of soluble HLA (sHLA molecules class II in saliva of MS patients can serve as marker of therapeutic response to high dose interferon beta-1a. Methods We measured the expression patterns of sHLA-II in saliva in 17 patients with relapsing/remitting MS and compared the results to clinical course and brain MRI. For comparison purposes we also assayed the saliva sHLA-II levels in 53 normal control subjects. Solid phase ELISA was used for measurement of sHLA-I and sHLA-II concentrations at baseline and after three and six months of treatment with high dose interferon beta-1a (IFN β-1a. Results The mean saliva sHLA-ll levels in MS patients was significantly higher than normal controls (354 ± 42 unit/mL vs. 222 ± 18 unit/mL, t= 8.16, p Conclusion Serial measurement of saliva sHLA-II may serve as a potential marker of therapeutic response to IFN β-1a. Larger clinical studies involving more RRMS patients over longer periods of time are needed to further test the significance and value of saliva sHLA-II as an accurate marker of therapeutic response to beta-interferons.

  8. Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns

    OpenAIRE

    Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; John D Reveille; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A.; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F.

    2015-01-01

    Objective Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. Methods We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were th...

  9. Mutational analysis of the HLA-DQ3.2 insulin-dependent diabetes mellitus susceptibility gene.

    Science.gov (United States)

    Kwok, W W; Lotshaw, C; Milner, E C; Knitter-Jack, N; Nepom, G T

    1989-01-01

    The human major histocompatibility complex includes approximately 14 class II HLA genes within the HLA-D region, most of which exist in multiple allelic forms. One of these genes, the DQ3.2 beta gene, accounts for the well-documented association of HLA-DR4 with insulin-dependent diabetes mellitus and is the single allele most highly correlated with this disease. We analyzed the amino acid substitutions that lead to the structural differences distinguishing DQ3.2 beta from its nondiabetogenic, but closely related allele, DQ3.1 beta. Site-directed mutagenesis of the DQ3.2 beta gene was used to convert key nucleotides into DQ3.1 beta codons. Subsequent expression studies of these mutated DQ3.2 beta clones using retroviral vectors defined amino acid 45 as critical for generating serologic epitopes characterizing the DQw3.1 beta and DQw3.2 beta molecules. Images PMID:2783780

  10. ANALYZING HLA HAPLOTYPE OF THE LOCI HLA-A, -B, AND -DRB1 IN MONGOLIA ETHNIC GROUP

    Institute of Scientific and Technical Information of China (English)

    Zhang Hongbo; Li Shengbin

    2006-01-01

    Objective To investigate HLA-A,-B and -DRB1 allele and HLA-A-B-DRB1 haplotype frequencies in Mongolia ethnic group. Methods HLA-A, -B, -DRB1 allele and haplotype in the Mongolia ethnic group were investigated based on 93 individuals by PCR- sequence-based typing (SBT) method. Results Twenty-one alleles were detected for HLA-A, 44 for HLA-B, and 26 for HLA-DRB1. The most frequent alleles were HLA-A*2402(0.2097), HLA-B*1302(0.0699), and HLA-DRB1*0701(0.1237). The most common HLA-A-B-DRB1 haplotype were A*3001-B*1302-DRB1*0701, A*0101-B*3701-DRB1*1001, followed by the A*0201-B*4601-DRB1*0901, A*2402-B*4801-DRB1*1101, A*2402-B*5201-DRB1*1501, A*3201-B*3503-DRB1*1301, and A*3303-B*5801-DRB1*0301, which were also presented in Chinese populations. Conclusion The data can be used in forensic and paternity tests to estimate the frequency of a DNA profile or anthropologic research. The characteristics of the distribution of HLA alleles revealed that Mongolia ethnic group is characterized by northern Mongolian Chinese.

  11. Paternal HLA-C and Maternal Killer-Cell Immunoglobulin-Like Receptor Genotypes in the Development of Autism

    Science.gov (United States)

    Gamliel, Moriya; Anderson, Karen L.; Ebstein, Richard P.; Yirmiya, Nurit; Mankuta, David

    2016-01-01

    Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal–fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents. This study enrolled 49 ASD children from different Israeli families, and their healthy parents. Among the parents, a higher frequency of HLA-C2 allotypes was found in the fathers, while its corresponding ligand 2DS1 was found in higher percentage in the maternal group. However, such skewing in KIR:HLA frequencies did not appear in the ASD children. Additionally, analysis of “overall activation” indicated higher activation in maternal than in paternal cohorts. PMID:27517034

  12. Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads

    DEFF Research Database (Denmark)

    Hylenius, Sine; Andersen, Anne-Marie Nybo; Melbye, Mads;

    2004-01-01

    that it is caused by immune- maladaptation. The MHC class Ib gene, HLA-G, is expressed in the placenta and seems to have immunomodulatory functions. Aberrant HLA-G mRNA and protein expression in pre-eclamptic placentas have been reported. Here, we have investigated detailed HLA-G genotypes in a case......-control study of 155 family triads of mother, father and newborn. Among primiparas, an overrepresentation of a homozygous HLA-G genotype was detected in the 40 pre-eclamptic offspring compared to the 70 controls [P = 0.002, Fisher's exact test; odds ratio 5.57 (95% CI 1.79-17.31)]. Further analyses suggested...... that the differences between pre-eclamptic cases and controls primarily were accomplished by a different transmission from the father of a 14 bp deletion/insertion polymorphism in exon 8 (P = 0.006, Fisher's exact test), which previously has been linked to differences in the levels of HLA-G expression...

  13. The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

    Directory of Open Access Journals (Sweden)

    Wester Eidi Nishimura

    2015-06-01

    Full Text Available OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers. RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions.

  14. Humanized HLA-DR4 mice fed with the protozoan pathogen of oysters Perkinsus marinus (Dermo do not develop noticeable pathology but elicit systemic immunity.

    Directory of Open Access Journals (Sweden)

    Wathsala Wijayalath

    Full Text Available Perkinsus marinus (Phylum Perkinsozoa is a marine protozoan parasite responsible for "Dermo" disease in oysters, which has caused extensive damage to the shellfish industry and estuarine environment. The infection prevalence has been estimated in some areas to be as high as 100%, often causing death of infected oysters within 1-2 years post-infection. Human consumption of the parasites via infected oysters is thus likely to occur, but to our knowledge the effect of oral consumption of P. marinus has not been investigated in humans or other mammals. To address the question we used humanized mice expressing HLA-DR4 molecules and lacking expression of mouse MHC-class II molecules (DR4.EA(0 in such a way that CD4 T cell responses are solely restricted by the human HLA-DR4 molecule. The DR4.EA(0 mice did not develop diarrhea or any detectable pathology in the gastrointestinal tract or lungs following single or repeated feedings with live P. marinus parasites. Furthermore, lymphocyte populations in the gut associated lymphoid tissue and spleen were unaltered in the parasite-fed mice ruling out local or systemic inflammation. Notably, naïve DR4.EA(0 mice had antibodies (IgM and IgG reacting against P. marinus parasites whereas parasite specific T cell responses were undetectable. Feeding with P. marinus boosted the antibody responses and stimulated specific cellular (IFNγ immunity to the oyster parasite. Our data indicate the ability of P. marinus parasites to induce systemic immunity in DR4.EA(0 mice without causing noticeable pathology, and support rationale grounds for using genetically engineered P. marinus as a new oral vaccine platform to induce systemic immunity against infectious agents.

  15. The role of class I histocompatibility antigens in the regulation of T-cell activation.

    OpenAIRE

    Dasgupta, J D; Cemach, K; Dubey, D P; Yunis, E J; Amos, D. B.

    1987-01-01

    Class I major histocompatibility antigens in humans (HLA antigens) were found to participate in the regulation of T-cell activation and proliferation induced by phytohemagglutinin. W6/32, a monomorphic antibody directed against class I HLA-A,B,C antigens, significantly inhibited the phytohemagglutinin-induced cell proliferation of peripheral blood lymphocytes. Almost complete suppression of cell activation was achieved on a subfraction of peripheral blood lymphocytes enriched in Mo1+ monocyte...

  16. Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules

    International Nuclear Information System (INIS)

    Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1 -specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null Hmy2CIR targets transfected with HLA-B35 but not HLA-B51, -Bw52, or -Bw53 transfected Hmy2CIR targets. These data demonstrated that the five amino acids substitutions on the α1 domain between HLA-B35 and -Bw53, which are associated with Bw4/Bw6 epitopes, play a critical role in the relationship of hmHA-1 to HLA-B35 molecules. The fact that the hmHA-1-specific CTLs failed to kill Hmy2CIR cells expressing HLA-B35/51 chimeric molecules composed of the α1 domain of HLA-B35 and other domains of HLA-B51 indicated that eight residues on the α2 domain also affect the interaction of hmHA-1 and the HLA-B35 molecules

  17. The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

    Directory of Open Access Journals (Sweden)

    Tomasz Skirecki

    2016-01-01

    Full Text Available Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p=0.01. The expression of CD64 on circulating and airway neutrophils was similar (p=0.47. Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p=0.031. Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization.

  18. The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

    Science.gov (United States)

    Mikaszewska-Sokolewicz, Małgorzata; Hoser, Grażyna; Zielińska-Borkowska, Urszula

    2016-01-01

    Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p = 0.01). The expression of CD64 on circulating and airway neutrophils was similar (p = 0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p = 0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization.

  19. HLA-DRB1 alleles in four Amerindian populations from Argentina and Paraguay.

    Science.gov (United States)

    Parolín, Maria L; Carnese, Francisco R

    2009-04-01

    The major histocompatibility complex (MHC) is one of the biological systems of major polymorphisms. The study of HLA class II variability has allowed the identification of several alleles that are characteristic to Amerindian populations, and it is an excellent tool to define the relations and biological affinities among them. In this work, we analyzed the allelic distribution of the HLA-DRB1 class II locus in four Amerindian populations: Mapuche (n = 34) and Tehuelche (n = 23) from the Patagonian region of Argentina, and Wichi SV (n = 24) and Lengua (n = 17) from the Argentinean and Paraguayan Chaco regions, respectively. In all of these groups, relatively high frequencies of Amerindian HLA-DRB1 alleles were observed (DRB1*0403, DRB1*0407, DRB1*0411, DRB1*0417, DRB1*0802, DRB1*0901, DRB1*1402, DRB1*1406 and DRB1*1602). However, we also detected the presence of non-Amerindian variants in Mapuche (35%) and Tehuelche (22%). We compared our data with those obtained in six indigenous groups of the Argentinean Chaco region and in a sample from Buenos Aires City. The genetic distance dendrogram showed a clear-cut division between the Patagonian and Chaco populations, which formed two different clusters. In spite of their linguistic differences, it can be inferred that the biological affinities observed are in concordance with the geographic distributions and interethnic relations established among the groups studied. PMID:21637670

  20. The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma.

    Science.gov (United States)

    Yang, Huimin; Yu, Kaihui; Zhang, Ruoheng; Li, Jiatong; Wei, Xiaomou; Zhang, Yuening; Zhang, Chengdong; Xiao, Feifan; Zhao, Dong; Lin, Xuandong; Wu, Huayu; Yang, Xiaoli

    2016-06-01

    Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities. PMID:27059731

  1. HLA-DRB1和HLA-DQB1基因与肿瘤的关联性研究%A relevance between tumor and HLA-DRB1 and HLA-DQB1 gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    周秀英; 于雅宁; 刘辉

    2013-01-01

    Objective To study the relevance between tumor and HLA-DRB1 and HLA-DQB1 gene polymorphism via analyzing 18 alleles of HLA-H gene locus of some tumor patients.Methods 18 alleles ofHLA-Ⅱ gene locus of 42 tumor patients were analyzed and compared.with those of 100 healthy people using PCR-SSP (polymerase chain reaction-sequence specific primers) technology.Results The HLA-DQB1 * 03 frequency of the tumor group was 65.5%,it was significantly higher than the 42.0% of the control group,RR =2.62,P <0.0001; the HLA-DQB1 * 06 frequency of tumor group was 10.7%,it was significantly lower than 24.0% of the control group,RR =0.38,P value was of 0.010.Condusion It is suggested that HLA-DQB1 * 03 may be the susceptibility gene of tumor,HLA-DQB1 * 06 may be the resistance genes of tumor.%目的 通过对42例肿瘤患者HLA-DRB1和HLA-DQB1座位的18个等位基因位点的检测,探讨HLA-DRB1和HLA-DQB1基因多态性与肿瘤的关联性.方法 采用PCR-SSP技术,检测42例肿瘤患者的HLA-DRB1和HLA-DQBI基因位点18个,并以100例健康人作为对照.结果 肿瘤HLA-DQB1* 03型频率的65.5%,高于对照组的42.0%,RR =2.62,P<0.0001;肿瘤组HLA-DQB1* 06型频率为10.7%,明显低于对照组的24.0%,RR =0.38,P=0.010.结论 HLA-DQB1* 03可能是肿瘤的易感基因,HLA-DQB1* 06可能是肿瘤的抗性基因.

  2. HLA TYPE IS NOT INDICATIVE FOR THE EFFECT OF THYMECTOMY IN MYASTHENIA-GRAVIS

    NARCIS (Netherlands)

    KUKS, JBM; LEMS, SPM; OOSTERHUIS, HJGH

    1992-01-01

    The frequency of HLA types in a selected group of 40 patients with myasthenia gravis in relation to the effect of thymectomy and also to gender, and thymus histology was studied. As generally described we found a significant increase in the frequency of HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 in the tot

  3. Head and neck squamous cell carcinoma susceptibility genes in the HLA region

    NARCIS (Netherlands)

    Reinders, Judith

    2006-01-01

    The Human Leukocyte Antigen (HLA) region on the short arm of chromosome 6 includes the classical HLA genes and in addition HLA-related and non-HLA related genes. The majority of the genes located in this region are directly or indirectly involved in the immune response. The polymorphic HLA molecules

  4. Human Leukocyte Antigen Associations with Humoral and Cellular Immunity Following a Second Dose of Measles-Containing Vaccine: Persistence, Dampening, and Extinction of Associations Found After a First Dose

    OpenAIRE

    Jacobson, Robert M.; Ovsyannikova, Inna G.; Vierkant, Robert A.; Pankratz, V. Shane; Poland, Gregory A.

    2011-01-01

    Previously we found Human Leukocyte Antigen (HLA) associations with humoral immunity following a single dose of measles-containing vaccine. In this study, we sought to determine if HLA associations exist with humoral and cellular immunity following a second dose of measles-containing vaccine and if the associations we found with humoral immunity after the first dose persist following a second dose.

  5. HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy.

    Science.gov (United States)

    Marincola, F M; Venzon, D; White, D; Rubin, J T; Lotze, M T; Simonis, T B; Balkissoon, J; Rosenberg, S A; Parkinson, D R

    1992-12-01

    Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy. PMID:1423301

  6. Weak association of anti-sperm antibodies and strong association of familial cryptorchidism/infertility with HLA-DRB1polymorphisms in prepubertal Ukrainian boys

    Directory of Open Access Journals (Sweden)

    Chopyak Valentyna

    2011-09-01

    Full Text Available Abstract Background Cryptorchidism is a frequent syndrome occurring in 1-2% of males within the first year of age. Autoimmune reactions, particularly directed to testicular elements and/or spermatozoa have been found to be often associated with cryptorchidism. Therefore we investigated in this study the frequency of HLA class II alleles in order to recognize possible genetic predisposition for antisperm antibodies development in prepubertal boys with diagnosed cryptorchidism in Caucasoid population. Methods Sixty prepubertal boys with cryptorchidism and sixty healthy boys were examined for anti-sperm antibodies by indirect immunobead test as well as for their HLA-DRB1 and -DQB1 alleles using DNA obtained from peripheral blood leukocytes. The typing of HLA-DRB1 and -DQB1 was performed by using PCR-SSP low resolution method. Results Allele frequencies of HLA-DRB1 and HLA-DQB1 did not differ between boys with cryptorchidism and control boys. However, weakly significant differences in DRB1*04 (p corrected = 0.0475 and DQB1*06 (p corrected = 0.0385 were seen between cryptorchid patients with and without AsA, but none of these two patient groups differed significantly in HLA class II frequencies from controls except for AsA-negatives and HLA-DQB1*06 (p corrected = 0.0247. On the other hand, comparison of cryptorchid boys with familial cryptorchidism and/or infertility to control boys revealed highly significant (p corrected = 0.0006 difference in HLA-DRB*11 frequency, whereas boys with sporadic cryptorchidism did not differ from control. A much weaker, but still significant difference in DRB*11 frequency was also observed between boys with bilateral cryptorchidism and controls (p corrected = 0.037, whereas patients with unilateral cryptorchidism were not different from control in frequency of any HLA-DRB1 or -DQB1 allele tested. Conclusions Predisposition to produce anti-sperm antibodies seems to be only weakly associated with HLA class II genes

  7. Association of HLA-DRB1 and HLA-DQB1 gene polymorphisms with pemphigus%HLA-DRB1和HLA-DQB1基因多态性与天疱疮的相关性

    Institute of Scientific and Technical Information of China (English)

    吴桂菊; 张勇; 朱海琴; 王颖; 潘萌

    2011-01-01

    Objective To explore the genetic association of human leucocyte antigen ( HLA) -DRB1 and HLA-DQB1 allele polymorphisms with pemphigus. Methods Fifty-eight patients with pemphigus ( case group) and 89 normal controls (control group) were selected in Shanghai as study objectives. HLA-DRB1 and HLA-DQB1 alleles in two groups were typed by polymerase chain reaction-sequence specific primers (PCR-SSP). Direct count method was adopted to calculate allele frequencies, and comparison was performed between groups. Odds ratios (OR) of allele frequencies were used to evaluate the association of gene with disease. Results A total of 13 HLA-DRB1 alleles and 5 HLA-DQB1 alleles were detected in case group and control group. The frequencies of HLA-DRB1 * 14 allele and HLA- DQB1 * 05 allele in case group were significantly higher than those in control group (17. 24% vs 1. 69% , P = 0. 000, Pc < 0. 05, OR = 12. 150; 18. 97% vs 6.74%, P = 0.001, Pc < 0.05, OR = 3. 238). The frequency of HLA-DQB1 * 06 allele in case group was significantly lower than that in control group (15.52% vs 30.90%, P=0.003, Pe<0.05, OR =0.411). Conclusion HLA-DRB1 * 14 and HLA-DQB1 * 05 may be predisposing genes, while HLA-DQB1 * 06 may be protective gene of pemphigus in Shanghai.%目的 探讨人白细胞抗原(HLA)-DRB1和HLA-DQB1等位基因多态性与天疱疮的遗传相关性.方法 以上海地区的58例天疱疮患者(病例组)和89名正常对照者(对照组)作为研究对象.采用聚合酶链反应-序列特异性引物分型技术(PCR-SSP)对两组HLA-DRB1和HLA-DQB1等位基因进行分型,直接计数法计算等位基因频率并进行组间比较,以等位基因频率的比值比(OR)评价基因与疾病的关联性.结果 病例组和对照组共检测到13种HLA-DRB1等位基因和5种HLA-DQB1等位基因.统计学分析结果表明:病例组HLA-DRB1*14和HLA-DQB1*05等位基因频率分别为17.24%和18.97%,显著高于对照组的1.69%(P=0.000,P值的校正值Pc<0.05,OR=12

  8. [The HLA system in the Moroccan population: General review].

    Science.gov (United States)

    Brick, C; Atouf, O; Essakalli, M

    2015-01-01

    The Moroccan population is an interesting study model of Human Leukocyte Antigen (HLA) polymorphism given its ethnic and genetic diversity. Through an analysis of the literature, this work proposes to establish a balance of knowledge for this population in the field of histocompatibility: HLA diversity, anthropology, transplantation and HLA associations and diseases. This analysis shows that the HLA system has not been fully explored within the Moroccan population. However, the results obtained allowed us to initiate a database reflecting the specific healthy Moroccan population HLA polymorphism to identify immigration flows and relationships with different people of the world and to reveal the association of certain HLA alleles with frequent pathologies. We also propose to analyze the reasons hindering the development of this activity in Morocco and we will try to identify some perspectives. PMID:26597780

  9. HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.

    OpenAIRE

    Khare, S D; Hansen, J.; Luthra, H S; David, C S

    1996-01-01

    MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta2-microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addit...

  10. Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27–restricted human immune response

    OpenAIRE

    Dazert, Eva; Neumann-Haefelin, Christoph; Bressanelli, Stéphane; Fitzmaurice, Karen; Kort, Julia; Timm, Jörg; McKiernan, Susan; Kelleher, Dermot; Gruener, Norbert; Tavis, John E.; Rosen, Hugo R.; Shaw, Jaqueline; Bowness, Paul; Blum, Hubert E.; Klenerman, Paul

    2009-01-01

    There is an association between expression of the MHC class I molecule HLA-B27 and protection following human infection with either HIV or HCV. In both cases, protection has been linked to HLA-B27 presentation of a single immunodominant viral peptide epitope to CD8+ T cells. If HIV mutates the HLA-B27–binding anchor of this epitope to escape the protective immune response, the result is a less-fit virus that requires additional compensatory clustered mutations. Here, we sought to determine wh...

  11. Cellular Automata

    OpenAIRE

    Bagnoli, Franco

    1998-01-01

    An introduction to cellular automata (both deterministic and probabilistic) with examples. Definition of deterministic automata, dynamical properties, damage spreading and Lyapunov exponents; probabilistic automata and Markov processes, nonequilibrium phase transitions, directed percolation, diffusion; simulation techniques, mean field. Investigation themes: life, epidemics, forest fires, percolation, modeling of ecosystems and speciation. They represent my notes for the school "Dynamical Mod...

  12. The TAG family of cancer/testis antigens is widely expressed in a variety of malignancies and gives rise to HLA-A2-restricted epitopes.

    Science.gov (United States)

    Adair, Sara J; Carr, Tiffany M; Fink, Mitsú J; Slingluff, Craig L; Hogan, Kevin T

    2008-01-01

    The TAG-1, TAG-2a, TAG-2b, and TAG-2c cancer/testis genes, known to be expressed in an unusually high percentage of melanoma cell lines, are shown here to be expressed in a variety of tumor lines of diverse histologic type, including cancers of the brain, breast, colon, lung, ovary, pharynx, and tongue. The genes are also expressed in fresh, uncultured melanoma, and ovarian cancer cells. Epitope prediction algorithms were used to identify potential HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 epitopes, and these potential epitopes were tested for their ability to stimulate a peptide-specific cytotoxic T lymphocyte response using lymphocytes from healthy donors. Two HLA-A2-restricted epitopes (SLGWLFLLL and LLLRLECNV) were identified using this approach. Cytotoxic T lymphocytes specific for each of these peptides were capable of recognizing tumor cells expressing both the corresponding class I major histocompatibility complex encoded molecule and the TAG genes. These results indicate that TAG-derived peptides may be good components of a therapeutic vaccine designed to target melanoma and a variety of epithelial cell-derived malignancies. PMID:18157007

  13. Separate Developmental Programs for HLA-A and -B Cell Surface Expression during Differentiation from Embryonic Stem Cells to Lymphocytes, Adipocytes and Osteoblasts

    DEFF Research Database (Denmark)

    Sabir, Hardee J; Nehlin, Jan O; Qanie, Diyako;

    2013-01-01

    A major problem of allogeneic stem cell therapy is immunologically mediated graft rejection. HLA class I A, B, and Cw antigens are crucial factors, but little is known of their respective expression on stem cells and their progenies. We have recently shown that locus-specific expression (HLA-A, but...... not -B) is seen on some multipotent stem cells, and this raises the question how this is in other stem cells and how it changes during differentiation. In this study, we have used flow cytometry to investigate the cell surface expression of HLA-A and -B on human embryonic stem cells (hESC), human...... hematopoietic stem cells (hHSC), human mesenchymal stem cells (hMSC) and their fully-differentiated progenies such as lymphocytes, adipocytes and osteoblasts. hESC showed extremely low levels of HLA-A and no -B. In contrast, multipotent hMSC and hHSC generally expressed higher levels of HLA-A and clearly HLA...

  14. HLA Genotyping and Antibody Characterization Using the Luminex™ Multiplex Technology

    OpenAIRE

    Heinemann, Falko Markus

    2009-01-01

    The Luminex-based human leukocyte antigen (HLA) antibody screening technology is widespread used in laboratories affiliated to kidney transplantation programs and enables both screening (i.e. the definition of positive or negative antibody status) and antibody identification with high sensitivity and specificity. HLA typing at different levels of resolution with Luminex technology uses sequence-specific oligonucleotide probes bound to color-coded microbeads in order to identify HLA alleles en...

  15. Associations of HLA alleles with specific language impairment

    OpenAIRE

    Nudel, Ron; Simpson, Nuala H; Baird, Gillian; O’Hare, Anne; Conti-Ramsden, Gina; Bolton, Patrick F.; Hennessy, Elizabeth R; Monaco, Anthony P; Knight, Julian C.; Winney, Bruce; Fisher, Simon E.; Newbury, Dianne F

    2014-01-01

    Background Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment. Methods We perf...

  16. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

    OpenAIRE

    Antoniou, Antony N.; Izabela Lenart; Guiliano, David B.

    2011-01-01

    The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs) which include ankylosing spondylitis (AS) and Reactive Arthritis (ReA), has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with...

  17. HLA-B27 Misfolding and Ankylosing Spondylitis

    OpenAIRE

    Colbert, Robert A.; Tran, Tri M.; Layh-Schmitt, Gerlinde

    2013-01-01

    Understanding how HLA-B27 contributes to the pathogenesis of spondyloarthritis continues to be an important goal. Current efforts are aimed largely on three areas of investigation; peptide presentation to CD8 T cells, abnormal forms of the HLA-B27 heavy chain and their recognition by leukocyte immunoglobulin-like receptors on immune effector cells, and HLA-B27 heavy chain misfolding and intrinsic biological effects on affected cells. In this chapter we review our current understanding of the ...

  18. The IMGT/HLA and IPD databases.

    Science.gov (United States)

    Robinson, James; Waller, Matthew J; Fail, Sylvie C; Marsh, Steven G E

    2006-12-01

    The IMGT/HLA database (www.ebi.ac.uk/imgt/hla) has provided a centralized repository for the sequences of the alleles named by the WHO Nomenclature Committee for Factors of the HLA System since 1998. Since its initial release, the database has rapidly grown in size and is recognized as the primary source of information for the study of sequences of the human major histocompatibility complex. The Immuno Polymorphism Database (IPD; www.ebi.ac.uk/ipd) is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD currently consists of four databases: IPD-KIR contains the allelic sequences of killer-cell immunoglobulin-like receptors; IPD-MHC is a database of sequences of the major histocompatibility complex of different species; IPD-HPA contains alloantigens expressed only on platelets (human platelet antigens or HPA); and IPD-ESTDAB provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. PMID:16944494

  19. Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patients with spondyloarthritis (SpA)

    NARCIS (Netherlands)

    N. Mahfoudh; M. Siala; M. Rihl; A. Kammoun; F. Frikha; H. Fourati; M. Younes; R. Gdoura; L. Gaddour; F. Hakim; Z. Bahloul; S. Baklouti; N. Bargaoui; S. Sellami; A. Hammami; H. Makni

    2011-01-01

    The aim of this study is to investigate the association of HLA-A, B and HLA-DR gene expression and to assess an association of additional HLA antigens besides HLA-B27 in south Tunisian patients with spondyloarthritis (SpA). Eighty-five patients diagnosed with ankylosing spondylitis (AS, n = 68) and

  20. HLA-B27 Positivity: associated health implications

    OpenAIRE

    Cox, C. L.; Gibbons, H.; Evans, P; Withers, T.; Titmus, K.

    2011-01-01

    HLA-B27 positivity makes the onset of autoimmune diseases such as uveitis, ankylosing spondylitis and Crohn's disease more likely to occur. Ankylosing spondylitis and Crohn's disease are two types of HLA-B27 positive diseases that demonstrate a direct association with uveitis. Although the possession of HLA-B27 positivity is not mandatory for autoimmune diseases such as uveitis to occur, HLA-B27 positivity not only makes it more likely but may modify the clinical picture in which a patient pr...

  1. Bartonella henselae associated uveitis and HLA-B27

    OpenAIRE

    Kerkhoff, F.T.; Rothova, A

    2000-01-01

    AIM—To investigate the frequency of HLA-B27 in patients with presumed Bartonella henselae associated uveitis and to describe the clinical characteristics of HLA-B27 positive patients with uveitis and presumed ocular bartonellosis (POB).
METHODS—The diagnosis of POB was considered in 19 patients with unexplained uveitis (except for the HLA-B27 association) and high positive IgG (titre ⩾1:900) and/or IgM (titre ⩾1:250) antibodies against B henselae. In addition to B henselae serology and HLA-B2...

  2. HLA-DP specific responses in allogeneic stem cell transplantation

    OpenAIRE

    Rutten, Caroline Elisabeth

    2013-01-01

    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, whereas a significant decreased risk of disease relapse was still observed. In this thesis we showed that HLA-DPB1 mismatched allo-SCT followed by donor lymp...

  3. Dynamic properties of cellular neural networks

    Directory of Open Access Journals (Sweden)

    Angela Slavova

    1993-01-01

    Full Text Available Dynamic behavior of a new class of information-processing systems called Cellular Neural Networks is investigated. In this paper we introduce a small parameter in the state equation of a cellular neural network and we seek for periodic phenomena. New approach is used for proving stability of a cellular neural network by constructing Lyapunov's majorizing equations. This algorithm is helpful for finding a map from initial continuous state space of a cellular neural network into discrete output. A comparison between cellular neural networks and cellular automata is made.

  4. Association of HLA-G 3' Untranslated Region Polymorphisms with Systemic Lupus Erythematosus in a Japanese Population: A Case-Control Association Study.

    Science.gov (United States)

    Hachiya, Yuki; Kawasaki, Aya; Oka, Shomi; Kondo, Yuya; Ito, Satoshi; Matsumoto, Isao; Kusaoi, Makio; Amano, Hirofumi; Suda, Akiko; Setoguchi, Keigo; Nagai, Tatsuo; Shimada, Kota; Sugii, Shoji; Okamoto, Akira; Chiba, Noriyuki; Suematsu, Eiichi; Ohno, Shigeru; Katayama, Masao; Kono, Hajime; Hirohata, Shunsei; Takasaki, Yoshinari; Hashimoto, Hiroshi; Sumida, Takayuki; Nagaoka, Shouhei; Tohma, Shigeto; Furukawa, Hiroshi; Tsuchiya, Naoyuki

    2016-01-01

    HLA-G plays a role in fetal-maternal tolerance as well as immunoregulation, and has been suggested to be involved in autoimmune diseases and cancers. HLA-G encodes two potentially functional polymorphisms in the 3' untranslated region, 14bp insertion/deletion (14bp indel, rs371194629) and a single nucleotide polymorphism rs1063320, previously reported to affect HLA-G expression level or splicing isoform and to be associated with susceptibility to systemic lupus erythematosus (SLE). However, the results of SLE association studies are inconsistent, probably due to the small sample size of each study and lack of consideration of linkage disequilibrium (LD) with HLA-class II haplotypes in each population. In this study, we performed association studies of these polymorphisms on 843 patients with SLE and 778 healthy controls in a Japanese population, in many of whom HLA-DRB1 alleles have been genotyped at the four-digit level. LD was detected between DRB1*13:02, protective against multiple autoimmune diseases in the Japanese, and the rs1063320 G (D' = 0.86, r2 = 0.02) and with 14bp del (D' = 0.62, r2 = 0.01), but not between SLE-susceptible DRB1*15:01 and HLA-G. Although significant association with overall SLE was not detected, 14bp ins allele was significantly associated with SLE with the age of onset RNP antibody and anti-Sm antibody positive SLE, which was dependent on negative LD with DRB1*13:02. eQTL analysis showed reduced HLA-G mRNA level in 14bp ins/ins individuals. In conclusion, our observations showed that HLA-G 14bp ins allele represents a genetic contribution on early-onset SLE independent of DRB1. PMID:27331404

  5. Killer Ig-like receptor 2DL4 does not mediate NK cell IFN-γ responses to soluble HLA-G preparations.

    Science.gov (United States)

    Le Page, Michael E L; Goodridge, Jodie P; John, Elisabeth; Christiansen, Frank T; Witt, Campbell S

    2014-01-15

    The MHC class Ib molecule HLA-G has previously been reported to be the ligand for the NK cell receptor killer Ig-like receptor (KIR)2DL4, but this remains controversial. In this study, we investigated IFN-γ production by freshly isolated NK cells in response to both soluble and solid-phase ligands, including anti-KIR2DL4 mAbs and rHLA-G. Although freshly isolated CD56(bright) NK cells produced IFN-γ in response to soluble HLA-G preparations, the response was found to be absolutely dependent on the presence of small numbers of contaminating CD56(-), CD14(-), CD11c(+) myeloid dendritic cells (mDCs). HLA-G tetramers bound only to the contaminating mDCs in the NK preparations, and Abs to KIR2DL4 and HLA-G did not block NK cell IFN-γ production. NK cells did not respond to plate-bound HLA-G. Freshly isolated NK cells also produced IFN-γ in response to unpurified soluble anti-KIR2DL4 mAb but not to low endotoxin affinity-purified Ab. The data suggest that previous reports of functional interactions between KIR2DL4 and HLA-G may have resulted from the use of purified NK cells that were contaminated with mDCs and HLA-G preparations that were contaminated with material capable of stimulating mDCs to produce cytokines that stimulate NK cells to produce IFN-γ. PMID:24337374

  6. Frequency determination of HLA-DRB1 and HLA-DQB1 alleles in children with primary vesicoureteral reflux

    Directory of Open Access Journals (Sweden)

    Mohammadreza Bazrafshani

    2014-12-01

    Conclusion: The HLA cluster might affect on susceptibility to vesicoureteral reflux es-pecially by locus which located close to HLA-DRB1 and HLA-DQB1 genes. This study demonstrates for the first time in Iran. However, further extensive researches with a large number of samples from different populations and ethnicities are required to val-idate the results obtained in this study.

  7. HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control

    DEFF Research Database (Denmark)

    Kløverpris, Henrik Nyhus; Buus, Anette Stryhn; van der Stok, Mary;

    2012-01-01

    The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together...... because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C......-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of...

  8. HLA-B27 typing in the categorisation of uveitis in a HLA-B27 rich population

    OpenAIRE

    Huhtinen, M; Karma, A

    2000-01-01

    AIMS—To determine whether HLA-B27 typing helps the clinician in the diagnostic examination of uveitis in a HLA-B27 rich population and also whether the clinical picture of HLA-B27 positive unilateral acute or recurrent anterior uveitis (AAU) is distinguishable from the idiopathic negative form.
METHODS—During a 3 year period 220 consecutive patients with undetermined uveitis at onset were examined in the Helsinki University Eye Clinic. HLA-B27 antigen was tested for 85% of the patients. Other...

  9. Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population.

    Science.gov (United States)

    Conde-Jaldón, Marta; Montes-Cano, Marco Antonio; García-Lozano, José Raul; Ortiz-Fernández, Lourdes; Ortego-Centeno, Norberto; González-León, Rocío; Espinosa, Gerard; Graña-Gil, Genaro; Sánchez-Bursón, Juan; González-Gay, Miguel Angel; Barnosi-Marín, Ana Celia; Solans, Roser; Fanlo, Patricia; Carballeira, Mónica Rodríguez; Camps, Teresa; Castañeda, Santos; Martín, Javier; González-Escribano, María Francisca

    2014-01-01

    Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population. PMID:25019531

  10. High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency.

    Directory of Open Access Journals (Sweden)

    Ricardo C Ferreira

    2012-01-01

    Full Text Available Selective IgA deficiency (IgAD; serum IgA<0.07 g/l is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10(-57; OR = 2.80 resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10(-17; OR = 4.28 and the DRB1*1501 (combined P = 2.24×10(-35; OR = 0.13 alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to

  11. Relationship between HLA-DQA1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    刘巍; 李为民; 孙宁玲

    2004-01-01

    Background Autoimmune mechanisms are likely to participate in the pathogenesis of subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class Ⅱ genes, especially highly polymorphic HLA-DQ genes, play an important role in the activation of immune responses, and thus control the predisposition for or protect from IDC. This study was conducted to investigate the HLA-DQA1 allele polymorphisms in IDC patients and to explore the underlying immunological mechanism and the hereditary susceptibility to IDC.Methods The polymerase chain reaction sequence-specific primers (PCR-SSP) technique was used to analyze the polymorphisms in the second exon of DQA1 in three groups: 72 IDC patients diagnosed according to the criteria of World Health Organization (IDC group); 100 end-stage heart failure patients suffering from a disease of known etiology (HF group); and 100 healthy subjects enrolled for the study during a routine health survey (control group). Patients in the IDC group were stratified according to ejection fraction (EF). Those with EF values were higher than 35% were placed into subgroup 1; subgroup 2 included patients with an EF value of 15%-35%; and subgroup 3 consisted of those whose EF values less than 15%. Results The frequency of HLA-DQA1*0501 alleles was significantly higher in the IDC group (0.39) than that in the HF group (0.12) and the control group (0.09) (both P<0.05). Further analysis of the three IDC subgroups showed a higher frequency of DQA1*0501 among patients with lower EF values (both P<0.05, compared with subgroups 1 and 2). The frequency of DQA1*0201 was higher in the control group than that in the IDC group (P<0.05).Conclusions The HLA-DQA1*0501 allele confers susceptibility to IDC, while the DQA1*0201 allele confers protection against it, which indicates that genetic background

  12. HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients.

    Science.gov (United States)

    Katarina, K; Daniela, P; Peter, N; Marianna, R; Pavlina, C; Stepanka, P; Jan, L; Ludmila, T; Michal, A; Marie, C

    2007-02-01

    Type 1 diabetes mellitus (T1DM) is one of the long-time studied autoimmune disorders. The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family. In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested. Patients were divided into the subgroups in relation to the disease type: T1DM in children, T1DM in adults, and Latent Autoimmune Diabetes in Adults (LADA). HLA-DRB1 (*)04 and HLA-DQB1 (*)0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively). HLA-DRB1 (*)03 has been found as a single risk factor for LADA (P<0.0001, OR=4.9). We detected 15 alleles for the NFKB1 gene polymorphism (CA-repeats) in the Czech population. The alleles were ranging in size from 114-142 bp corresponding to 10-25 CA repeats. Frequency of the A7 allele of NFKB1 gene has been significantly increased in T1DM adults (P<0.01). There was no difference in A and a G allele frequency of NFKBIA gene between the control group and patients, but the association of the AA genotype of NFKBIA gene has been found for LADA (P<0.05). Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course. Due to the results obtained in the epidemiological study we have been looking also for the function significance of the genetic predisposition. No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background. PMID:17318773

  13. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  14. Acute human herpesvirus-6A infection of human mesothelial cells modulates HLA molecules.

    Science.gov (United States)

    Caselli, Elisabetta; Campioni, Diana; Cavazzini, Francesco; Gentili, Valentina; Bortolotti, Daria; Cuneo, Antonio; Di Luca, Dario; Rizzo, Roberta

    2015-09-01

    Human herpesvirus 6A (HHV-6A) causes ubiquitous infections and has been associated with several diseases in immunosuppressed and immune dysregulated individuals. Although considered a lymphotropic virus, HHV-6A has the potential to infect many cell types, inducing important alterations in the infected cell. In our search for additional potential targets for HHV-6A infection, we analyzed the susceptibility of human mesothelial cells to viral infection. HHV-6A infection was performed and analyzed on primary human mesothelial cells isolated from serous cavity fluid, infected in vitro with a cell-free HHV-6A inoculum. The results demonstrated that mesothelial cells are susceptible to in vitro HHV-6A infection, and more importantly, that the virus induces an alteration of HLA expression on the cell surface, inducing HLA class II and HLA-G de novo expression. Since mesothelial cells play a pivotal role in many processes, including inflammation and antigen presentation, we speculate that, in vivo, this virus-induced perturbation might be correlated to alterations in mesothelium functions. PMID:26085284

  15. KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Alessandro Soria

    Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

  16. HLA and skin cancer HLA e câncer de pele

    Directory of Open Access Journals (Sweden)

    Renan Rangel Bonamigo

    2012-02-01

    Full Text Available Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.Os cânceres da pele - melanoma e não-melanoma - são neoplasias comuns e com incidência crescente ao longo de décadas. Representam um importante problema de saúde pública. A patogênese destas neoplasias não é completamente compreendida, assim como não o são os fatores genéticos envolvidos. Os genes HLA estão associados a alguns tumores e podem representar um dos mecanismos implicados no desenvolvimento do câncer de pele. Apresenta-se uma revisão atualizada sobre a relação entre antígenos HLA, câncer da pele não-melanoma e melanoma.

  17. Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins

    DEFF Research Database (Denmark)

    Rognan, D; Lauemoller, S L; Holm, A; Buus, S; Tschinke, V

    1999-01-01

    A simple and fast free energy scoring function (Fresno) has been developed to predict the binding free energy of peptides to class I major histocompatibility (MHC) proteins. It differs from existing scoring functions mainly by the explicit treatment of ligand desolvation and of unfavorable protein...... interactions were found to contribute the most to HLA-A0201-peptide interactions, whereas H-bonding predominates in H-2K(k) recognition. Both cross-validated models were afterward used to predict the binding affinity of a test set of 26 peptides to HLA-A0204 (an HLA allele closely related to HLA-A0201) and of...

  18. Polymorphism of exon 3 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Meldgaard, M; Sørensen, Steen; Morling, N

    1997-01-01

    rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...

  19. Isolated HLA-B27 associated Achilles tendinitis.

    OpenAIRE

    I. Olivieri; Gemignani, G; Gherardi, S; Grassi, L.; M.L. Ciompi

    1987-01-01

    The case of a 37 year old man with a longstanding HLA-B27 associated bilateral Achilles tendinitis without seronegative spondyloarthropathy is reported. This case suggests that heel enthesopathy may for a long time be the only clinical manifestation of the HLA-B27 associated disease process.

  20. Architecture of HLA Based Distributed Virtual Geographic Environment

    Institute of Scientific and Technical Information of China (English)

    XU Bingli; LIN Hui; GONG Jianhua

    2006-01-01

    Integrating the theory of distributed virtual geographic environment (DVGE) and high level architecture(HLA), the architecture of DVGE based on HLA is designed. The data flow and the object models of the architecture are also discussed. The architecture basically meets the need of DVGE in real-time communication, distribution, collaboration, reusing and interoperation, expansion, and standard.

  1. Cellular resilience.

    Science.gov (United States)

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  2. Concerted In Vitro Trimming of Viral HLA-B27-Restricted Ligands by Human ERAP1 and ERAP2 Aminopeptidases

    OpenAIRE

    Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

    2013-01-01

    In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. ...

  3. HLA antigens in psoriasis and psoriatic arthritis.

    OpenAIRE

    Woodrow, J. C.; Ilchysyn, A

    1985-01-01

    HLA phenotypes were determined in 50 patients with psoriasis alone and in 50 patients with psoriasis and psoriatic arthritis. Positive associations were found in both groups with B13, B17, B37, Cw6, and DR7, and in addition with C4A6. Higher relative risks were found in respect to the patients with psoriasis alone compared with those with arthritis, and this suggests the involvement of additional genetic factors predisposing to peripheral arthritis. In patients with psoriasis only, the presen...

  4. Structural analysis of an HLA-B27 functional variant, B27d detected in American blacks

    International Nuclear Information System (INIS)

    The structure of a new functional variant B27d has been established by comparative peptide mapping and radiochemical sequencing. This analysis complete the structural characterization of the six know histocompatibility leukocyte antigen (HLA)-B27 subtypes. The only detected amino acid change between the main HLA-B27.1 subtype and B27d is that of Try59 to His59. Position 59 has not been previously found to vary among class I HLA or H-2 antigens. Such substitution accounts for the reported isoelectric focusing pattern of this variant. HLA-B27d is the only B27 variant found to differ from other subtypes by a single amino acid replacement. The nature of the change is compatible with its origin by a point mutation from HLB-B27.1. Because B27d was found only American blacks and in no other ethnic groups, it is suggested that this variant originated as a result of a mutation of the B27.1 gene that occurred within the black population. Structural analysis of B27d was done by comparative mapping. Radiochemical sequencing was carried out with 14C-labeled and 3H-labeled amino acids

  5. Structural analysis of an HLA-B27 functional variant, B27d detected in American blacks

    Energy Technology Data Exchange (ETDEWEB)

    Rojo, S.; Aparicio, P.; Hansen, J.A.; Choo, S.Y.; Lopez de Castro, J.A.

    1987-11-15

    The structure of a new functional variant B27d has been established by comparative peptide mapping and radiochemical sequencing. This analysis complete the structural characterization of the six know histocompatibility leukocyte antigen (HLA)-B27 subtypes. The only detected amino acid change between the main HLA-B27.1 subtype and B27d is that of Try/sub 59/ to His/sub 59/. Position 59 has not been previously found to vary among class I HLA or H-2 antigens. Such substitution accounts for the reported isoelectric focusing pattern of this variant. HLA-B27d is the only B27 variant found to differ from other subtypes by a single amino acid replacement. The nature of the change is compatible with its origin by a point mutation from HLB-B27.1. Because B27d was found only American blacks and in no other ethnic groups, it is suggested that this variant originated as a result of a mutation of the B27.1 gene that occurred within the black population. Structural analysis of B27d was done by comparative mapping. Radiochemical sequencing was carried out with /sup 14/C-labeled and /sup 3/H-labeled amino acids.

  6. Rational design of class I MHC ligands

    Science.gov (United States)

    Rognan, D.; Scapozza, L.; Folkers, G.; Daser, Angelika

    1995-04-01

    From the knowledge of the three-dimensional structure of a class I MHC protein, several non natural peptides were designed in order to either optimize the interactions of one secondary anchor amino acid with its HLA binding pocket or to substitute the non interacting part with spacer residues. All peptides were synthesized and tested for binding to the class I MHC protein in an in vitro reconstitution assay. As predicted, the non natural peptides present an enhanced binding to the HLA-B27 molecule with respect to their natural parent peptides. This study constitutes the first step towards the rational design of non peptidic MHC ligands that should be very promising tools for the selective immunotherapy of autoimmune diseases.

  7. The asymmetric protein expression hypothesis - Explaining the unilaterality of HLA-B27-positive acute anterior uveitides.

    Science.gov (United States)

    Clarke, Margo S; Plouznikoff, Alexandre; Deschênes, Jean

    2016-03-01

    For reasons still unclear, most HLA-B27-positive acute anterior uveitides occur unilaterally. Building upon the growing literature showing that left-right asymmetry exist at the biomolecular and at the cellular levels, we propose a new hypothesis to explain why HLA-B27-positive acute anterior uveitides tend to affect one eye selectively. We postulate that left and right uveal tissue may present quantitatively and qualitatively different proteins to the immune system, capable to trigger an autoimmune response, and that other variables, including anatomical, cellular and molecular barriers, as well as our own eye-derived immunological tolerance and immune suppressive intraocular microenvironment may also be unequally distributed, and impact differently the immune privileges of the left and right eye. These same quantitative and qualitative differences might also explain why HLA-B27-positive acute anterior uveitides can flip-flop between the left and the right eye, after the first attack. By trying to figure out why one eye is targeted by an autoimmune reaction while the other is clinically unaffected, we might be able to better understand how and why an autoimmune reaction starts. Hopefully, this will help us devise better treatments for ocular autoimmune diseases, and contribute to the management of autoinflammatory conditions with a marked asymmetric clinical presentation in other fields. PMID:26880626

  8. The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection

    Science.gov (United States)

    Sullivan, Lucy C.; Westall, Glen P.; Widjaja, Jacqueline M. L.; Mifsud, Nicole A.; Nguyen, Thi H. O.; Meehan, Aislin C.; Kotsimbos, Tom C.; Brooks, Andrew G.

    2015-01-01

    The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical peptide sequence with that found in the leader sequence of many human leukocyte antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40 specific T cells by tetramer staining of peripheral blood mononuclear cells (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however the magnitude of the response varied significantly between patients. Moreover, unlike healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that minor histocompatibility antigens presented by HLA-E can represent an additional risk factor following lung transplantation. PMID:26302084

  9. Analysis of allele frequencies of HLA-DRB1 * 12 : 01 : 01G and HLA-DRB1 * 14 : 01 : 01G groups%HLA-DRB1*12:01:01G和HLA-DRB1*14:01:01G组内等位基因频率的统计分析

    Institute of Scientific and Technical Information of China (English)

    何俊俊; 章伟; 和艳敏; 王炜; 韩浙东; 陈男英; 朱发明; 吕杭军; 严力行

    2012-01-01

    目的 区分并计算人类白细胞抗原(human leukocyte antigen,HLA) HLA-DRB1* 12:01:01G(HLA-DRB1* 12:01:01/12:06/12:10/12:17)和HLA-DRB1* 14:01:01G(DRB1* 14:01:01/14:54)组内等位基因及其相对频率,并分析其与HLA-DRB3和HLA-DQB1的连锁情况.方法 收集115例HLA-DRB1*12:01:01G组和108例HLA-DRB1*14:01:01G组标本,采用单核苷酸序列分析(polymerase chain reaction-sequence based typing,PCR-SBT)方法检测HLA-DRB1* 12:01:01G组等位基因的第1~3外显子序列和HLA-DRB1* 14:01:01G组的第2、3外显子序列.HLA-DRB3和HLA-DQB1基因分型采用PCR-SBT方法.结果 115例HLA-DRB1* 12:01:01G组标本中,101例(87.8%)为HLA-DRB1* 12:01:01,14例(12.2%)为HLA-DRB1* 12:10,未发现HLA-DRB1* 12:06和HLA-DRB1* 12:17. 108例HLA-DRB1*14:01:01G组标本全部为HLA-DRB1*14:54. HLA-DRB1*12:01:01与HLA-DRB3* 01:01:02和HLA-DQB1* 03:01连锁,HLA-DRB1* 12:10则与HLA-DRB3* 02:02:01和HLA-DQB1* 03:01连锁.HLA-DRB1* 14:54与HLA-DRB3* 02:02:01和HLA-DQB1* 05:02、*05:03连锁.结论 HLA-DRB1* 12:01:01G组中HLA-DRB1* 12:01:01频率最高,而HLA-DRB1* 14:01:01G组则以HLA-DRB1* 14:54频率最高.%Objective To discriminate and analyze the relative frequencies of alleles in HLA-DRB1 * 12:01:01G(HLA-DRB1 * 12:01:01 /12:06/12:10/12:17) and HLA-DRB1 * 14:01:01G (DRB1 * 14:01:01/14:54) groups and assess their associations with HLA-DRB3 and HLA-DQB1 loci.Methods A total of 115 DNA samples previously typed as HLA-DRB1 * 12:01:01G and 108 samples from HLA-DRB1 * 14:01:01G were selected.DNA sequences for exons 1 to 3 of the HLA-DRB1 locus were analyzed for HLA-DRB1 * 12:01:01G,and exons 2 to 3 were analyzed for HLA-DRB1 * 14:01:01G by polymerase chain reaction sequence-based typing (PCR-SBT).Genotyping of HLA-DRB3 and HLA-DQB1 were achieved by PCRSBT.Results Among 115 samples previously typed as HLA-DRB1 * 12:01:01G,101 (87.8%) were confirmed as HLA-DRB1 * 12:01:01 and 14 (12.2%) were HLA-DRB1 * 12:10,but HLA-DRB1 * 12:06 and HLA-DRB1 * 12

  10. Lack of expression of HLA-B27 gene in transgenic mouse trophoblast. Conserved genetic pressures underlying extra-embryonic development

    OpenAIRE

    1989-01-01

    The mechanisms that regulate developmental control of the expression of MHC class I genes during generation of extra-embryonic tissues are largely unknown. In the present study, we studied the levels of transcripts of the human HLA-B27 gene in extra-embryonic tissues of transgenic mice containing the HLA-B27 (heavy chain) gene by in situ hybridization with biotinylated single-stranded RNA probes. In contrast to extra-embryonic stromal cells and embryonic tissues which contain (varying levels ...

  11. Identification of a polymorphic variant associated with HLA-DQw3 and characterized by specific restriction sites within the DQ beta-chain gene.

    OpenAIRE

    Kim, S J; Holbeck, S. L.; Nisperos, B; J. A. Hansen; Maeda, H.; Nepom, G T

    1985-01-01

    Restriction endonuclease digestion of genomic DNA from 24 lymphoblastoid cell lines homozygous for the HLA class II specificity DQw3, followed by hybridization with a DQ beta-chain cDNA probe, identified a genomic polymorphism with variable BamHI and HindIII recognition sites. This restriction fragment pattern was found for several haplotypes associated with the DQw3 specificity, including some haplotypes positive for the HLA-DR specificities DR4, DR5, DRw8, and DRw12. The variant fragment pa...

  12. 肝细胞癌组织中HLA-DR,-DQ的表达及其意义%Expression of HLA-DR and HLA-DQ in Hepatocellular Carcinoma and its Significance.

    Institute of Scientific and Technical Information of China (English)

    李宏涛; 肖文华; 李秋文; 郝怡鑫; 朱建华; 王如良; 叶明

    2011-01-01

    Objective To study the expression of HLA - DR and HLA - DQ antigens in hepatocellular carcinoma ( HCC ) and its significance. Methods The expression of HLA - DR and HLA - DQ antigens in human 38 HCCs cases were detected with immunohistochemistry, then the relations between the expression of genes with clinical and pathology parameters ( such as cancerous differentiation and metastasis and others) were analyzed by Chi square test. Results The immunoreactivity of HLA - DR and - DQ proteins were mainly distributed in cytoplasm of cancerous cells, the positive rate of HLA - DR and DQ expression were 5. 3% (2/35 ) and 92. 1% ( 35/38) respectively. HLA - DR was related with gender of HCC patients, HLA - DQ was positive relation with non - lymphatic metastasis of HCC (P <0.0001 ). Conclusion HLA - DQ expression is very common in HCCs; The absence of HLA - DQ expression may contribute to lymphnodes metastasis in HCC.%目的 探讨人白细胞抗原(HLA)-DR和-DQ分子在肝细胞癌的表达及其意义.方法 采用免疫组化法分别检测HLA-DR和HLA-DQ抗原在38例人肝癌组织芯片中的表达情况,并和临床病理资料进行相关性分析.结果 肝癌组织中HLA-DR和HLA-DQ抗原信号主要定位于细胞浆.HLA-DR的阳性率为5.3%(2/38),HLA-DQ的阳性率为92.1%(35/38),但在4例伴淋巴结转移的肝癌中,3例无HLA-DQ的表达,HLA-DQ表达与肝癌的淋巴结转移负相关(P<0.0001).HLA-DR和HLA-DQ表达与年龄和肝癌的组织分化无相关性(P>0.05).结论 HLA-DQ的表达在肝癌组织中很常见,无HLA-DQ的表达可能提示与淋巴结转移有关.

  13. Donor-reactive cytokine profiles after HLA-identical living-related kidney transplantation

    NARCIS (Netherlands)

    J.H. Gerrits (Jeroen); J. van de Wetering (Jacqueline); J.J. Drabbels (Jos); F.H.J. Claas (Frans); W. Weimar (Willem); N.M. van Besouw (Nicole)

    2008-01-01

    textabstractBackground. After HLA-identical living-related (LR) kidney transplantation, only non-HLA antigen mismatches between donor and recipient may exist. We questioned whether donor-reactive responses against non-HLA antigens could be found after HLA-identical LR kidney transplantation, and won

  14. HLA polymorphism of the Zhuang population reflects the common HLA characteristics among Zhuang-Dong language-speaking populations

    Institute of Scientific and Technical Information of China (English)

    Li SHI; Katsushi TOKUNAGA; Jia-you CHU; Xiao-qin HUANG; Lei SHI; Yu-fen TAO; Yu-feng YAO; Liang YU; Ke-qin LIN; Wen YI; Hao SUN

    2011-01-01

    A study of the human leukocyte antigen (HLA) genetic characteristics in the Zhuang, the largest ethnic population in China, would provide insight into Zhuang history and give a useful tool for disease associations, transplantation, and anthropology. In the present study, we report the comprehensive HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles and haplotypes in the Zhuang population of southern China for the first time. A total of 13 HLA-A, 24 HLA-B, 22 HLA-C, and 18 HLA-DRB1 were identified in 104 Zhuang individuals. The frequencies of HLA-A*11:01, A*02:07, A*24:02, A*02:03, and A*33:03 on A loci, B*15:02, B*58:01, B*46:01, and B*13:01 on B loci, C*03:04, C*08:01, C*01:02, C*03:02, and C*07:02 on C loci, and DRB1*15:01, DRB1*16:02, DRB1*14:01, DRB1*15:02, and DRB1*03:01 on the DRB1 loci were >10%. The A*33:03-C*03:02-B*58:01-DRB1*03:01 and A*02:07-C*01:02-B*46:01-DRB1*14:01 haplotypes were predominant in the Zhuang. The phylogenetic tree, as well as the analysis of haplotypes, suggested that the Zhuang are genetically similar to southern Chinese populations, especially the Zhuang-Dong language-speaking populations, such as the Bouyei, Dai, and Maonan. Even though the Zhuang and southern Chinese populations shared common alleles and haplotypes, the Zhuang has maintained its unique genetic characteristics.

  15. An HLA-C amino-acid variant in addition to HLA-B*27 confers risk for ankylosing spondylitis in the Korean population

    OpenAIRE

    Kim, Kwangwoo; Bang, So-Young; Lee, Seunghun; Lee, Hye-Soon; Shim, Seung-Cheol; Kang, Young Mo; Suh, Chang-Hee; Sun, Celi; Nath, Swapan K; Bae, Sang-Cheol; Kim, Tae-Hwan

    2015-01-01

    Introduction The presence of the HLA-B*27 allele is a major risk factor for the development of ankylosing spondylitis (AS), which causes chronic inflammation of the spine and other sites. We investigated residual effects outside HLA-B within the major histocompatibility complex (MHC) region in the Korean population. Methods Using the Korean HLA reference panel, we inferred the classic HLA alleles and amino-acid residues of the six HLA genes (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) and MHC sin...

  16. 原发性肾病综合征与HLA-A、HLA-B、HLA-DRB1基因相关性的研究%The correlation study of alleles of HLA-A, HLA-B and HLA-DRB1 in patients with idiopathic nephrotic syndrome

    Institute of Scientific and Technical Information of China (English)

    樊晓光; 杨菲; 张德梅; 阎冰

    2007-01-01

    目的 探讨HLA-A、HLA-B、HLA-DRB1位点基因与山西汉族激素抵抗肾病综合征(SRNS)的相关性.方法 用聚合酶链反应序列特异性引物法,对30例SRNS患者(成人22例,儿童8例)和45例正常对照者进行了HLA-A、HLA-B、HLA-DRB1等位基因分型,并分析了A、B、DRB1基因在各组的分布.结果 SRNS患者组HLA-B*15、B*44基因频率较正常对照组增高(P<0.05);成人SRNS患者组HLA-DRB1*07、B*44基因频率较正常对照组增高(P<0.05),成人SRNS患者组HLA-DRB1*15基因频率较正常对照组降低(P<0.05);儿童SRNS患者组HLA-DRB1*10基因频率较正常对照组增高(P<0.05).结论 SRNS发病可能与HLA-B*15、B*44基因有关,成人SRNS发病可能与HLA-DRB1*07、B*44基因有关,HLA-DRB1*15对成人SRNS发病可能有保护作用,儿童SRNS发病可能与HLA-DRB1*10基因有关;HLA与SRNS的相关性不仅与人种、国家和地区有关,还可能与发病年龄有关.

  17. Study on polymorphisms of HLA-A, HLA-B and HLA-DRB1 loci among HIV long-term nonprogressors in Lishui%丽水市HIV感染长期不进展者HLA-A、HLA-B和HLA-DRB1基因多态性的研究

    Institute of Scientific and Technical Information of China (English)

    叶灵; 雷永良; 陈沙彬; 叶碧峰; 陈秀英

    2015-01-01

    目的 从基因水平了解丽水市艾滋病病毒(HIV)感染长期不进展者(LTNPs)与典型进展者(TPs)的人类白细胞抗原(HLA)-A、HLA-B和HLA-DRB1位点等位基因频率,比较两类人群的差异,初步探索保护性基因和易感基因.方法 应用聚合酶链反应-序列特异性引物技术(PCR-SSP),对丽水市42例LTNPs和48例TPs进行HLA-A、HLA-B和HLA-DRB1等位基因分型.结果 共鉴定出9个HLA-A等位基因,16个HLA-B等位基因,12个HLA-DRB1等位基因.HLA-A* 02频率LTNPs组(44.05%)高于TPs组(20.83%)(P<0.01),而A*11频率则是LINPs组(20.24%)低于TPs组(42.71%) (P<0.01);HLA-B* 40频率LTNPs组(17.86%)低于TPs组(28.13%) (P>0.05);HLA-DRB* 15频率LTNPs组(5.95%)低于TPs组(29.17%) (P<0.01);LTNPs组HLA基因座纯合子频率(15.87%)低于TPs组(33.33%)(P<0.01).结论 在该人群中,HLA-A* 02等位基因可能与延缓艾滋病疾病进程相关,而HLA-A* 11、B* 40、DRB1* 15可能加速艾滋病疾病进程.含HLA基因杂合子者对疾病显示出更好的抵御能力.

  18. Post-transcriptional and epigenetic regulation of antigen processing machinery (APM components and HLA-I in cervical cancers from Uighur women.

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    Ayshamgul Hasim

    Full Text Available Normal function of human leukocyte antigen class I (HLA-I and antigen processing machinery (APM proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen presentation, mainly due to the deregulation in HLA-I and APM expression or function. The posttranscriptional regulation of HLA-I and APM expression may associate with epigenetic modifications in cancer development which was not described so far. Here we showed that the development of cervical intraepithelial neoplasia (CIN and cervical squamous cell carcinoma (CSCC in Uighur women was accompanied with the partial or total loss of protein expression of HLA-I, ß2-m and APM components, including the transporter associated with antigen processing (TAP1/2, low molecular mass protein (LMP2, LMP7, endoplasmic reticulum aminopeptidase 1(ERAP1, chaperone molecules include calreticulin (CLR, calnexin (CNX and ERp57, and this was proved again by analysis of transcription of the same genes in addition to three genes HLA-A, B and C coding for HLA-I. By bisulfite sequencing approach, we identified target CpG islands methylated at the gene promoter region of TAP1, TAP2, LMP7, tapasin and ERp57 in cervical carcinoma cells. Further analysis of CpG site specific methylation of these genes in cases of CSCC and CIN demonstrated an inverse correlation of altered CpG island methylation of TAP1, LMP7, and ERp57 with changes in protein expression. Moreover, promoter methylation of these genes was significantly higher in cases positive for human papillomavirus 16 (HPV 16 than negative ones. Our results suggested that epigenetic modifications are responsible for the aberrant expression of certain HLA-I and APM genes, and may help to understand unrevealed mechanisms of tumor escape from immune surveillance in cervical carcinogenesis.

  19. Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8+ T-cell responses in HLA-A2.1/Kb transgenic mice.

    Science.gov (United States)

    Zhang, Yuxia; Li, Shu; Shan, Ming; Pan, Xuwen; Zhuang, Ke; He, Lihua; Gould, Keith; Tien, Po

    2007-05-01

    The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single-chain trimers (SCT) composed of peptide epitope beta2-microglobulin (beta2m) and major histocompatibility complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)-A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C(18-27) and C(107-115). Transfection of NIH-3T3 cells with pcDNA3.0-SCT-C(18-27) and SCT-C(107-115) leads to stable presentation of HBcAg epitopes at the cell surface. HLA-A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg-specific CTL responses by enzyme-linked immunospot assay (ELISPOT) and in vitro interferon-gamma release experiments. HBcAg-specific CTLs from vaccinated HLA-A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA-A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA-A2-positive HBV carriers. PMID:17244158

  20. HLA region excluded by linkage analyses of early onset periodontitis

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    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.