INTACT PROTEINS CAN BIND TO CLASS-II HISTOCOMPATIBILITY MOLECULES WITH HIGH-AFFINITY

The ability of intact protein antigens to bind to purified class II hi stocompatibility molecules was investigated. Intact bovine ribonucleas e (RNase) inhibited peptide binding to DR1 with a potency similar to t hat of a high affinity peptide or irreversibly denatured RNase. Simila rly, horse myoglobin (Mb) was a potent inhibitor of peptide binding to I-E-k. I-E-k-Mb complexes were directly visualized as a distinct band with reduced mobility on SDS-PAGE. Direct binding experiments with bi otin-labeled proteins demonstrated that Mb and RNase bind to class II molecules through the peptide-binding groove with high affinity, and t hat binding occurs in the absence of detergent. The possibility that H LA-DM can catalyse the binding of intact protein antigens was supporte d by the observation that DM enhances the binding of biotin-RNase to D R1. Our results provide further support for the hypothesis that intact , partially unfolded protein antigens can act as ligands for initial i nteraction with class II molecules. (C) 1997 Elsevier Science Ltd.