Do the peptide-binding properties of diabetogenic class II molecules explain autoreactivity?

One seminal aspect in autoimmune diabetes is antigen presentation of beta cell antigens by the diabetes-propensity class II histocompatibility molecules. The binding properties of I-Ag7 molecules are reviewed here and an emphasis is placed on their selection of peptides with a highly specific sequence motif, in which one or more acidic amino acids are found at the carboxy end interacting at the P9 anchoring site of I-Ag7. The reasons for the central role of I-Ag7 in the autoimmune response are analyzed. The insulin B chain segment 9–23 is a hot spot for T cell selection and a striking example of a weak MHC binding peptide that triggers autoreactivity.