title: Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.
abstract: We have determined the crystal structure of I-Ag7, an integral component in murine type I diabetes development. Several features distinguish I-Ag7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-Ag7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-Ag7 epitope HEL(11-25) support a comprehensive structure-based I-Ag7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-Ag7 in autoimmunity.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Latek
authors.forename: A
authors.initials: A
authors.lastname: Suri
authors.forename: S J
authors.initials: SJ
authors.lastname: Petzold
authors.forename: C A
authors.initials: CA
authors.lastname: Nelson
authors.forename: O
authors.initials: O
authors.lastname: Kanagawa
authors.forename: E R
authors.initials: ER
authors.lastname: Unanue
authors.forename: D H
authors.initials: DH
authors.lastname: Fremont
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D002645:Chickens; D018360:Crystallography, X-Ray; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D019281:Dimerization; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D010455:Peptides; D009113:Muramidase