An insulin peptide that binds an alternative site in class II major histocompatibility complex

We report that a peptide from the B chain of insulin, B(10-30), binds with high affinity to multiple class II proteins, including IA(b,d,k), IE(d,k), and DR1. The ability of B(10-30) to inhibit the binding oi other peptide antigens to class II does not correlate with its affinity for class II. B(10-30) only weakly inhibits the binding of antigenic peptides. Conversely, peptides with high affinity for the peptide-binding groove of various class II proteins do not inhibit B(10-30) binding. The rate of association of B(10-30) with class II is unusually rapid, approaching saturation in 1-2 h compared with 1-2 d for classical peptide antigens in the same conditions. The dissociation rate is also relatively rapid, The B(10-30) peptide inhibits the binding of the superantigen staphylococal enterotoxin B (SEE) to IA(k). It also inhibits SEB-mediated T cell activation, These observations support the conclusion that B(10-30) binds to a site outside the peptide-binding groove, Out findings indicate that short-lived peptide-class II complexes can be formed through interactions involving the SEE-binding site and raise the possibility that alternative complexes may serve as T cell receptor ligands.