title: Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase.
abstract: 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.
authors.affiliation: Virginia Mason Research Center, Seattle, WA 98101, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Kwok
authors.forename: M L
authors.initials: ML
authors.lastname: Domeier
authors.forename: F C
authors.initials: FC
authors.lastname: Raymond
authors.forename: P
authors.initials: P
authors.lastname: Byers
authors.forename: G T
authors.initials: GT
authors.lastname: Nepom
mesh_terms: 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
chemical_list: D000939:Epitopes; D006683:HLA-DQ Antigens; C051569:HLA-DQ3 antigen; D010455:Peptides; D005968:Glutamate Decarboxylase