T cell recognition of human pre-proinsulin peptides depends on the polymorphism at HLA DQ locus: A study using HLA DQ8 and DQG transgenic mice

被引:41
作者
Raju, R
Munn, SR
David, CS [1 ]
机构
[1] Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Div Transplantat Surg, Rochester, MN 55905 USA
关键词
D O I
10.1016/S0198-8859(97)00212-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
HLA DQ8 (DQ A1*0301/DQB1*0302) molecule is implicated in the susceptibility to insulin dependent diabetes mellitus whereas, HLA DQ6 (DQ A1*0103/DQB1*0601) molecule may have a protective effect. In this study we used mice transgenic to HLA DQ8 and HLA-DQ6 to elucidate the T cell determinants on a putative islet cell target antigen, insulin. These mice do not express endogenous mouse class II heterodimers on cell surface. Using overlapping synthetic peptides spanning the complete sequence of human pre-proinsulin, we identified the sequences recognized by T cells in DQ8 transgenic mice and compared these to those in DQ6 transgenic mice. We observed a differential pattern of recognition of epitopes on human pre-proinsulin (HPI) polypeptide presented by the HLA DQ8 allele as compared to HLA DQ6. The sequences 1-24 and 44-63 were immunodominant in DQ8 transgenic mice while DQ6 transgenic mice primarily recognized sequences 14-33 and 74-93 of HPI. We found that the immune response generated in HLA DQ8 transgenic mice against HPI 1-24 cross-reacted to the mouse pre-proinsulin sequence 1-24. The T cell response were specifically inhibited using anti-CD4 and anti-DQ8 monoclonal antibodies. This cross-recognition of self sequences raises the possibility of modulation of experimental diabetes using this peptide. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc.
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页码:21 / 29
页数:9
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