Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase

作者：William W. Kwok, Mary Ellen Domeier, F C Raymond, Patricia Marie Byers, Gerald T. Nepom · 发表于：The Journal of Immunology · 年份：1996 · DOI：10.4049/jimmunol.156.6.2171 · 被引用次数：140 · 研究领域：Diabetes and associated disorders、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Polymorphic residues of HLA class II molecules influence immune activation in part by determining specific structural constraints for binding antigenic peptides. We identified a peptide from glutamic acid decarboxylase, a diabetes-associated autoantigen that preferentially bound to HLA-DQ3.2 molecules, one of the HLA determinants highly associated with insulin-dependent diabetes. We analyzed interactions of specific HLA-DQ residues with modified peptide analogues and found a pattern of permissive site-specific amino acids that accommodated allele-specific binding. Four anchor residues constrain binding to different DQ alleles; limited variation at two of these sites, residues 4 and 9, accounts for the unique pattern of peptide binding to HLA-DQ3.1 or HLA-DQ3.2.