The effect of diabetogenic peptides on the conformation of the MHC class II molecule I-A(g7) in type 1 diabetes

Type 1 diabetes is strongly associated with particular alleles of MHC class II molecules, and in mouse models, it is associated with a single class II molecule, I-Ag7. Structural polymorphisms unique to the I-Ag7 beta-chain affect the repertoire of peptides that I-Ag7 may bind. This class II molecule binds and displays a wide variety of peptides at the surface of cells; however, only certain peptides in the context of I-Ag7 generate autoimmune responses. Previous studies have demonstrated that peptides can induce different conformations in I-Ag7 that are functional at the cell surface. In the current study, we determined that diabetogenic peptides induce distinct conformations in I-Ag7. Our data suggests that diabetogenic and non-diabetogenic peptides induce different conformations. These peptide-induced conformations may be important for T cell receptor binding and recognition by T cells.