Enhancement of monoclonal antibodies against HLA-A2 is due to antibody bivalency.

Enhancement between two monoclonal antibodies directed against the same antigen is when binding of one antibody, the enhancing antibody, increases the measured binding of the other antibody. This phenomenon has been observed for monoclonal antibodies against a variety of molecules including histocompatibility antigens. The mechanism of enhancement for monoclonal antibodies against HLA-A2 has been studied with purified preparations of IgG, F(ab')2 and Fab. Enhancement was only observed between antibodies against different antigenic sites. It requires bivalency of both antibody species and involves formation of stable, cyclic, tetramolecular complexes consisting of two antigen molecules and one each of the two antibody molecules. Conformational changes of either antigen or antibody do not appear to be important in this system, nor is the formation of combinatorial determinants between antigen and enhancing antibody. The enhancing properties of the antibodies studied are adequately explained in terms of their affinities and association and dissociation constants.