The class II MHC I-Ag7 molecules from non-obese diabetic mice are poor peptide binders.
The class II molecules of the diabetes-prone NOD mice, I-Ag7, showed very limited amounts of stable form when analyzed by SDS-PAGE. We included the analysis of spleen B cells and B lymphoma cells transfected with I-Ag7 genes. Early during bio-synthesis there was invariant chain binding to the alpha beta-chains. Examination of APCs from F1 mice (NOD x C57BL/6) indicated that the same APC expressed high levels of unstable I-Ag7 and normal amounts of stable class II molecules compared with the other haplotype (I-Ab). The half-life of I-Ag7-peptide complexes on the cell surface of APC was significantly shorter than that of other class II haplotypes. Direct biochemical demonstration of peptide interactions with I-Ag7 was difficult to demonstrate. In T cell assays, the immunogenic peptides, including the diabetogenic Ag, were rapidly lost when peptide-pulsed APCs were washed free of peptide. We hypothesize that the weak and unstable peptide-binding property of I-Ag7 molecules does not favor the elimination or inactivation of autoreactive T cells.
Carrasco-Marin
E
E
Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Shimizu
J
J
Kanagawa
O
O
Unanue
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005802:Genes, MHC Class II; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD / Q000276:immunology*; D016513:Mice, SCID; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D010446:Peptide Fragments; D012967:Sodium Dodecyl Sulfate