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.