The study of molecular mimicry using combinatorial libraries can further the understanding of the specific recognition between molecules. We have screened synthetic combinatorial libraries composed of peptides, peptidomimetics, and nonpeptides against a variety of acceptor molecules to find mimics of their native ligands. This effort has included extensive epitope mapping studies for a number of antigen-antibody interactions. In these studies the antigenic determinants recognized by the antibodies have been correctly identified. Peptides having higher affinities than the original antigenic sequence have also been identified. These studies have revealed that monoclonal antibodies exhibit a broad range of specificities (polyspecificity), from antibodies that recognize only conservative substitutions of the epitope to antibodies that recognize antigens with high affinities that are completely unrelated to the parent antigen. Specific examples for anti-peptide, anti- protein and anti-carbohydrate antibodies will be presented. This work was funded by Trega Biosciences Inc, and US Army (DADMD17-94-J-4110).
