ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02585.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02586.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02587.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Previous studies showed the human MHC class I heavy chain HLA‐B*7301 has a sequence very divergent from other class I alleles. Despite the unusual sequence, we predicted B*7301 would retain the peptide‐binding function typical of other HLA‐A, B and C glycoproteins, and sequence similarity to B*2705 in a region of the peptide‐binding site known as the B pocket suggested B*7301 would bind peptides with Arg at position 2. To test this hypothesis, the peptide‐binding specificity of B*7301 was investigated. Sequence analysis of peptides bound endogenously by B*7301 indeed found selectivity for nonamer peptides possessing Arg at position 2 and a preference for small nonpolar residues such as Pro or Ala at the C terminus was also revealed. B*7301 therefore possesses the potential to function as a conventional antigen presenting class I glycoprotein. Functional similarities between B*7301 and B*2705 are discussed in the context of the association of B*27 subtypes with susceptibility to ankylosing sponylitis and arthritic

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02588.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

B*2703 is an exceptional HLA‐B27 molecule in that it differs from the most common B*2705 subtype by a unique amino acid change (His59) altering N‐terminal peptide anchorage. To assess how this unusual feature affects the antigenic structure of HLA‐B27, TCR usage by alloreactive CTL raised against B*2703 from two individuals was analyzed. Only few CTL recognized B*2703 but not or at a lower level B*2705. Limited heterogeneity of these CTL was revealed by: 1) identity of TCR in two pairs of such CTL clones, 2) identity of β chains, paired to distinct α chains, in two clonotypes, and 3) almost identical fine specificity of these two clonotypes with site‐specific HLA‐B27 mutants. These results indicate that B*2703 “private” epitopes are rare. TCR usage among anti‐B*2703 CTL was analogous as in anti‐B*2705 responses in the predominant and donor‐independent usage of Vβ segments from homology subgroup 4, more moderate and donor‐dependent Vα skewing, N+Dβ diversity limited by motifs shared among clonotypes, and restricted Jα heterogeneity. Homology of N+Dβ motifs and Jα segments of anti‐B*2703 with anti‐B*2705 TCR suggested significant sharing of peptide‐associated epitopes between both subtypes. The results indicate that allospecific TCR are recruited by B*2703 following similar rules as in the anti‐B*2705 response, and suggest that the B*2703 change keeps unaltered much of the antigenic structure of the molecule relative to B*2705. Therefore, most of the peptides bound to B*2703 should be the same and kee

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02589.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Japanese cedar pollinosis is a type I allergic disease caused by Japanese cedar (Cryptomeria japonica) pollen. We investigated the association between the disease and HLA class II alleles by HLA‐DNA typing using a PCR‐SSOP method and found that the frequency of HLA‐DP5 (DPA1*02022 and DPB1*0501) was significantly increased in the patients. To investigate whether the HLA‐DP5 molecule is directly involved in the pathogenesis of the disease, Japanese cedar pollen antigen (CPAg)‐specific T cell lines wereestablished from 3 patients who possessed HLA‐DP5(DPA1*02022/DPB1*0501). By using these CPAg‐specific T cell lines and HLA class II‐expressing L‐cell transfectants, we found that disease‐associated HLA‐DP5 restricted T cells specific for CPAg existed in the patients. Furthermore, among 38 synthesized overlapping peptides spanning the entire length of one of the major Japanese cedar pollen allergens, Cry j 1, an immunodominant peptide which induced HLA‐DP5 restricted Th2 was identified. These observations suggest that the HLA‐DP5 may be involved, at least in part, in the pathogenesis, by helping the IgE antibod

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02590.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In a family with a maternal DR/GLO recombination, cellular DP typing showed it to be located between DR and DP. RFLP studies done during the 9th international histocompatibility workshop gave anomalous segregation patterns of DPA and DPB bands that could be interpreted as being due to a second, paternal DR/DP recombination. This assumption was confirmed later by PCR‐SSO typing. A more precise mapping has been done by new markers showing the maternal recombination to be within the TAP2 locus and the paternal recombination to be between DQB1 and DQB3. This supports earlier suggestions of a hot spot of recombination in the TAP region. The recombinations involve parental haplotypes that presently show DR/DP linkage disequilibrium in the French population and it is proposed that DR/DP recombinations occur randomly while B/DR recombinations preferentially occur on haplotypes without strong linkage disequilibrium. Existing DR/DP linkage disequilibria in a given population will thus be broken down with time. The mixed lymphocyte culture response towards an isolated DP difference was tested in this and another DR/DP recombinant family. It showed that an alloresponse towards DP may be highly variable and this suggests that it might be important to define the rules for the strength of this reaction and the possible implications for allotransplantatio

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02591.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

HLA‐class I genes are the most polymorphic genetic system yet known. The polymorphic substitutions are mostly located in exon 2 and 3, encoding α1 and α2 domains, respectively, which are involved in peptide binding and T cell receptor interaction. In this study, we present the sequences of the introns neighboring the polymorphic exons in humans with few examples from non‐human primates. In general, intron sequences are found to be less polymorphic than the adjacent exons, displaying numerous locus‐specific and group‐specific sites. These sequences will provide important information for developing DNA based typing strategies for HLA‐clas

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02592.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Serology has been routinely used for class I HLA typing for the selection of donors for allotransplantation. However, serology is not adequate for the assignment of all class I specificities especially when testing non‐Caucasians subjects and it is necessary to adopt new strategies for routine testing. At the present time the extent of incorrect serologic HLA‐A assignments in clinical testing is not known. The polymerase chain reaction (PCR) based techniques have become useful standard clinical typing methods of HLA class II alleles but most laboratories still use serology for class I typing. In this report we have compared two PCR based techniques, PCR amplification with sequencespecific primers (PCR‐SSP) and PCR amplification and subsequent hybridization with sequence‐specific oligonucleotide probes (PCR‐SSOP), for the assignment of HLA‐A specificities in 56 blood samples from patients and families serologically typed for HLA‐A. This side‐by‐side comparison of PCR methods showed 100% correlation between them. However, serology showed 7.1% misassignments and, in an additional panel of 19 cells where serology produced equivocal results, the PCR‐SSP and SSOP methods identified the correct HLA‐A specificity. Our results emphasize the need to complement routine serologic testing of HLA specificities with a small number of primers designed to test HLA‐A34, A36, A43, A66, A74 and A80, that are not detected with high precision by serology. We concluded that the PCR‐SSP and ‐SSOP methods can be used in routine HLA‐A typing of patients and donors for transplantation with a gr

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02593.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A system for intermediate level identification of the HLA‐B locus alleles was devised. This system can be extended to identify individual alleles in any sample. The first step used primers which amplify all HLA‐B alleles. This amplicon was subjected to SSOP hybridization to allow intermediate level typing of samples. In the second step, group‐specific primers were utilized to obtain specific amplification of groups consisting of a few alleles. The oligotypes within each group were identified by the use of SSOP. The separation of groups of alleles by amplification allowed the use of a limited number of probes to identify oligotypes present in a sample. Additional probes can be added as new alleles are identified, increasing the flexibility of the system. HLA typing software was developed to determine the resolution of the system and to identify HLA oligotypes. PCR‐SSOP methods are in wide use and have been extensively validated. The procedures reported here will be relatively easy to implement for large‐scale DNA‐based typing of the

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02594.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY