Epitopes described in "A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes."

Article Authors:A L Corper; T Stratmann; V Apostolopoulos; C A Scott; K C Garcia; A S Kang; I A Wilson; L Teyton
Article Title:A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes.
Reference Detail
Reference ID:1007203
Abstract:Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.
Reference Type:Literature
PubMed ID:10775108
Journal Volume:288
Article Pages:505-11
Journal ISSN:1095-9203
Article Chemical List:Histocompatibility Antigens Class II;I-A g7 antigen;Peptide Library;Receptors, Antigen, T-Cell;Recombinant Proteins;Aspartic Acid;Glutamate Decarboxylase
Article MeSH List:Alleles; Amino Acid Motifs; Amino Acid Sequence; Animals; Aspartic Acid(chemistry); Crystallography, X-Ray; Diabetes Mellitus, Type 1(immunology); Drosophila melanogaster; Genes, MHC Class II; Glutamate Decarboxylase(metabolism); Histocompatibility Antigens Class II(chemistry; genetics; metabolism); Humans; Hydrogen Bonding; Mice; Mice, Inbred NOD; Models, Molecular; Molecular Sequence Data; Peptide Library; Protein Binding; Protein Conformation; Protein Structure, Secondary; Receptors, Antigen, T-Cell(metabolism); Recombinant Proteins(chemistry; metabolism)
Curation Last Updated:2015-07-30 20:20:22