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 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.
Kwok
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WW
Virginia Mason Research Center, Seattle, WA 98101, USA.
Domeier
M L
ML
Raymond
F C
FC
Byers
P
P
Nepom
G T
GT
D000483:Alleles; D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation
D000939:Epitopes; D006683:HLA-DQ Antigens; C051569:HLA-DQ3 antigen; D010455:Peptides; D005968:Glutamate Decarboxylase