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 o ther 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-bind ing groove of various class II proteins do not inhibit B(10-30) bindin g. The rate of association of B(10-30) with class II is unusually rapi d, approaching saturation in 1-2 h compared with 1-2 d for classical p eptide antigens in the same conditions. The dissociation rate is also relatively rapid, The B(10-30) peptide inhibits the binding of the sup erantigen staphylococal enterotoxin B (SEE) to IA(k). It also inhibits SEB-mediated T cell activation, These observations support the conclu sion 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 rai se the possibility that alternative complexes may serve as T cell rece ptor ligands.