ALLELE-SPECIFIC MOTIFS CHARACTERIZE HLA-DQ INTERACTIONS WITH A DIABETES-ASSOCIATED PEPTIDE DERIVED FROM GLUTAMIC-ACID DECARBOXYLASE

Polymorphic residues of HLA class II molecules influence immune activa tion in part by determining specific structural constraints for bindin g antigenic peptides, We identified a peptide from glutamic acid decar boxylase, 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-specifi c binding, Four anchor residues constrain binding to different D allel es; limited variation at two of these sites, residues 4 and 9, account s for the unique pattern of peptide binding to HLA-DQ3.1 or HLA-DQ3.2.