摘要:

Abstract:HLA‐A2 is present at high frequency in most populations, as identified by serological and biochemical means. The value of these methods is limited by their failure to discriminate between the products of the 14 known allelic HLA‐A*02 variants. The great majority of genetic polymorphism which defines the allelic variants is found in exons 2 and 3 of the A*02 genes. These exons encode the α‐1 and α‐2 domains of the HLA Class I molecules, and variation within the genes may influence the peptide binding specificity of the gene products of each allele. Failure to accurately assign the allelic types has implications in transplantation, in interpretation of cellular assays and in the understanding of HLA disease associations. We have developed a method for determining the 14 Known alleles of HLA‐A*02 by use of ARMS–PCR to determine the degree of variation of HLA‐A*02 alleles in 3 different population groups. Considerable variation was found in the relative frequencies of particular A*02 alleles between Caucasian, oriental and black individuals. Our results indicate the importance of ethnic origin in terms of the expected HLA‐A*02 allelic profile, and emphasize the functional significance of allele supecific subt

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02444.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Modifications have been introduced to a previously reported HLA‐B PCR‐SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were, three donors whose type differed from the serological t

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02445.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The high polymorphism of the HLA system has been used as a powerful genetic tool to single out individuals and populations. By studying characteristic allele frequencies and extended HLA haplotypes in different populations, it is possible to identify ethnic groups and establish the genetic relationships among them. In the present study, HLA‐A, ‐B, ‐C, ‐DR and ‐DQ typing at the serological/antigenic and the DNA level has been used for the first time to assign specific HLA frequencies and haplotypes to Spaniards and Basques and compare them with frequencies in other populations, particularly with North Africans. Allelic frequencies do not significantly differ between Spaniards and Basques. HLA genetic distances and their respective dendrogram together with the results on complete HLA haplotypes place Basques and Spaniards closer to paleo‐North African populations than to other Europeans. This goes in favour of the Basques being a relative genetic isolate coming from the primitive Iberian/paleo‐North African people. In addition, a tentative assignment of the most common Spanish HLA haplotypes to the different people who populated Iberia according to historical records

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02446.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Previous studies have reported associations between HLA antigens and Idiopathic IgA Nephropathy (IgAN). Nevertheless most of the studies were performed by serology. Thus we decided to perform the HLA class II typing of 58 patients by molecular biology techniques. We report a small increase of DRB1*04. But the main result of our study is the identification of a strong association between HLA DQB1*0301 and IgAN patients with an unfavorable outcome.

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02447.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:To study epitopes of HLA class II molecules, four mouse monoclonal antibodies (mAbs) 13B6, 17F8, 19A1 and 12G6 were made using HLA‐DQ8, DP2 and DP4 expressing mouse transfectants for immunization. Three of the mAbs, 13B6, 17F8 and 19A1, bound to all DQ1, 4, 8 or 9 positive B‐lymphoblastoid cell lines (B‐LCLs) and transfectants tested, i.e. cells carrying the DQB1 genes 0302‐3, 0401‐2, 0501‐3, 0601‐4 and 0609 irrespective of the accompanying DQA1 gene. These DQB1 genes code for the shared amino acids (aa) GVY in position 45–47 of the DQ β chain. DQ1+4+8+9 specific (IIB3) and DQ3 specific (IVD12) reference mAbs inhibited binding of all three mAbs. Testing 13B6, 17F8 and 19A1 with cells made using aa substitutions in various positions of DQP1*0302 indicated involvement of aa 45 in the epitopes of all three mAbs. The last mAb (12G6) bound to all B–LCLs and all DP transfected cells. However, only some DR transfectants and a single DQ transfectant (carrying DQA1 *0201 and DQB1*0202) bound mAb 12G6. This reactivity pattern correlates with a shared sequence of aa (RFDSDVGE) in position 39–46 of DR‐and DQ‐

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02448.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Polymorphism in the 5′‐upstream regulatory region of the DQA1 gene has been recently described. Using PCR‐SSO method and SSCP analysis we have investigated this polymorphism in a group of 111 Italian blood donors which had been oligotyped for DRB1, DQA1 and DQB1 genes. Eight allelic variants were detected. Looking at the relationships among QAP sequences and DQA1 and DRB1 genes, three alternative situations were found: 1. a one‐to‐one relation between QAP and DQA1 alleles, independently of the other class II genes; 2. the same QAP allele in association with different DQA1‐DRB1 haplotypes; 3. the same DQA1 allele with different QAP sequences according to the DRB1 specificity. No unexpected associations with DQB1 gene were found. These results must be interpreted considering that DQA1 and DRB1 genes are transcribed in opposite directions so that the promoter region of DQA1 gene lies between DQA1 and DRB1, close to the former but several hundreds kb away from

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02449.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:HLA‐DPB1 alleles were studied in 51 normal individuals and 93 leprosy patients from North India using a PCR‐oligotyping technique. Hybridization patterns could identify 47 alleles of which 20 were found in the population studied. DPB1*0401 was found to be the most frequent allele with a frequency of 66.7% followed by DPB1*0402 (21.6%), DPB1*0201 (21.6%), DPB1*1301 (15.7%) and DPB1*0301 (13.7%). Besides the common alleles, DPB1*0101, *1701, *2601, *1001, *1601, *0901, *2901, *1501, *0501, *1401, and *3301 were observed at low frequencies. DPB1*2101, DPB1*2801, DPBP3201 and DPB1*3501 were not found in the normal individuals studied but were observed in the group of leprosy patients. DPB1*0202, *0601, *0801 and *1101 were not found in this population. Two alleles with apparent new hybridization patterns were isolated and sequenced. The nucleotide sequences obtained have confirmed the hybridization patterns. One of them (DPB1 * 4601) confirms a sequence recently reported. The other has been given the official designation of DPB1*5

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02450.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Rheumatoid arthritis (RA) occurs more frequently in HLA‐DR4+individuals than in those who do not express this MHC class II molecule. Although the role of this genetic factor in the immunopathology of this autoimmune disease is unclear, the association of RA with HLA‐DR4 may indicate that DR4 molecules present autoantigen(s) to T cells. Here we report the analysis of naturally processed peptides, eluted from a mixture of HLA‐DR4Dw4 (DRB1*0401) and DR53 (DRB4* 0101) molecules isolated from an RA patient‐derived EBV‐transformed B cell line. Several (size variants of) self‐peptides originating from the autologous molecules HLA‐A2, HLA‐Cw9, HLA‐B62, HLA‐DR4Dw4 and HLA‐DR53, were identified. We also found a sequence that has no homology to any protein in the SwissProt protein sequence databank, and a peptide identical to an internal fragment of the autoantigen calreticulin. The association of the identified peptides with cells expressing HLA‐DR4Dw4/DR53 was confirmed by peptide binding analysis. In agreement with previously described peptide binding motifs for DR4Dw4, most peptides contained an aromatic residue (Phe, Tyr, Trp) at relative position i and a small hydroxyl‐containing residue (Ser, Thr) at i+5. Our findings indicate that in RA patient‐derived EBV‐transformed B cells DR4Dw4/ DR53 molecules present a peptide from the autoantigen calreticulin. Interestingly, autoantibodies against calreticulin have been found in various rheumatic diseases, including rheumatoid arthritis. Thus, the analysis of HLA class II‐bound peptides can lead to the identification of putative T helper epitopes, which might be involved in the immunop

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02451.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02452.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1995.tb02453.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY