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HLA Class I Alleles (hla + class_i_allele)
Selected AbstractsExtensive HLA class I allele promiscuity among viral CTL epitopesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Nicole Frahm Abstract Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. [source] Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia,,§HEPATOLOGY, Issue 5 2010Mark H. Kuniholm Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1,2.6), B*5701 (PR=2.0; 95% CI = 1.0,3.1), B*5703 (PR = 1.7; 95% CI = 1.0,2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0,3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2,0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2,11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. Conclusion: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized. (HEPATOLOGY 2010.) [source] Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over timeMICROBIOLOGY AND IMMUNOLOGY, Issue 4 2010Michiko Koga ABSTRACT HLA class I allele types have differential impacts on the level of the pVL and outcome of HIV-1 infection. While accumulations of CTL escape mutations at population levels have been reported, their actual impact on the level of the pVL remains unknown. In this study HLA class I types from 141 untreated, chronically HIV-1 infected Japanese patients diagnosed from 1995,2007 were determined, and the associations between expression of individual HLA alleles and level of pVL analyzed. It was found that the Japanese population has an extremely narrow HLA distribution compared to other ethnic groups, which may facilitate accumulation of CTL escape mutations at the population level. Moreover while they uniquely lack the most protective HLA-B27/B57, they commonly express the alleles that are protective in Caucasians (A11:10.4%, A26:11.55%, B51:8.6% and Cw14:12.7%). Cross-sectional analyses revealed no significant associations between expression of individual alleles and the level of the pVL. The patients were then stratified by the date of HIV diagnosis and the analyses repeated. It was found that, before 2001, B51+ individuals displayed significantly lower pVL than the other patients (median: 5150 vs. 18 000 RNA copies/ml, P= 0.048); however thereafter this protective effect waned and disappeared, whereas no changes were observed for any other alleles over time. These results indicate that, at a population level, some HLA alleles have been losing their beneficial effects against HIV disease progression over time, thereby possibly posing a significant challenge for HIV vaccine development. However such detrimental effects may be limited to particular HLA class I alleles. [source] Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapyPROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2007Iñaki Alvarez Abstract HLA class I molecules present peptides on the cell surface to CD8+ T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients. [source] Polymorphic Alu Insertions and their Associations with MHC Class I Alleles and Haplotypes in the Northeastern ThaisANNALS OF HUMAN GENETICS, Issue 4 2005D. S. Dunn Summary Polymorphic Alu insertions (POALINs) are known to contribute to the strong polymorphic nature of the Major Histocompatibility Complex (MHC). Previous population studies on MHC POALINs were limited to only Australian Caucasians and Japanese. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and -B associations, and the three and four locus alpha block POALIN haplotype frequencies in the Northeastern (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest positive associations between the POALINs and HLA class I alleles was between AluyMICB and HLA-B*57, AluyHJ and HLA-A*24 and HLA-A*01, and AluyHG and HLA-A*02, supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes were found more frequently than multiple POALIN haplotypes. However, of the seven different POALIN haplotypes within the MHC alpha block, there were only two significant differences between the NE Thais, Caucasians and Japanese. This study confirms that the MHC POALINs are in linkage disequilibrium with HLA-A and ,B alleles and that there are significant frequency differences for some of the POALINs when compared between NE Thai, Caucasians and Japanese. [source] Killer immunoglobulin-like receptor ligand HLA-Bw4 protects against multiple sclerosis,ANNALS OF NEUROLOGY, Issue 6 2009Åslaug R. Lorentzen MD Objective Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. A human leukocyte antigen (HLA) class II association is well established (DRB1*1501-DQB1*0602), but more recently HLA class II,independent associations with HLA class I variants have also been reported. The HLA class I (HLA-A, -B, -C) molecules serve as ligands for both T-cell receptors and killer immunoglobulin-like receptors (KIRs). We investigated the HLA class I alleles defined by their KIR binding motifs and the KIR genes to evaluate whether these genes could influence MS susceptibility or severity, alone or in combination. Methods We typed Norwegian MS patients (n = 631) and controls (n = 555) for HLA-A, -B, -C and -DRB1 alleles as well as the presence or absence of genes encoding inhibitory (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL5, KIR3DL1, KIR3DL2, KIR3DL3) and activating (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DL4, KIR2DS4, KIR2DS5, KIR3DS1) KIRs. Results The frequency of the HLA-Bw4 specificity, which is the ligand for the inhibitory KIR3DL1, was significantly reduced in MS patients as compared with controls (41.4% vs 55.1%, puncorrected (uc) = 4.6 × 10,6). Also after stratifying for known HLA class II associations, the HLA-Bw4 association was seen (puc = 0.002). No significant differences in gene carrier frequencies of inhibitory and activating KIRs were observed. However, our data indicate that MS patients who carry the activating KIR2DS2 and the inhibitory KIR2DL2 genes have more severe disease than patients not carrying these genes. Interpretation Carriage of the ligand of the inhibitory KIR3DL1 receptor, HLA-Bw4, was found to protect against MS in an HLA-DRB1 independent manner. Ann Neurol 2009;65:658,666 [source] Association of ankylosing spondylitis with HLA,B*1403 in a West African populationARTHRITIS & RHEUMATISM, Issue 11 2002Carlos López-Larrea Objective To investigate the contribution of HLA class I alleles in the susceptibility to primary ankylosing spondylitis (AS) in West African patients living in Togo. Methods A large epidemiologic analysis of 9,065 West African rheumatology patients living in Togo was performed in order to identify those who had AS. Eight Togolese patients with AS were identified. HLA was typed by polymerase chain reaction using sequence-specific oligonucleotide probes. DNA typing was also performed on a control population of 85 healthy subjects matched for ethnic background. Results A significant association between AS and B*14 was identified. This allele was found in 62.5% of the AS patients (odds ratio 69), but was carried by only 2% of the healthy controls. Analysis for B14 subtypes showed that B*1403 was the predominant allele in AS patients (odds ratio 171), and that this allele was absent in healthy controls. B27 was virtually absent, being observed in only 1 AS patient (B*2705). Conclusion HLA,B*1403 shows the B27 "supertype" motif and may exert an effect on AS susceptibility according to the arthritogenic peptide model. The association of B*1403 with AS has not previously been reported in either population. [source] | |||||||||||||