Interference of monoclonal antibodies with proteolysis of antigens in cellular and in acellular systems.

Monoclonal antibodies complexed with protein antigens can interfere with proteolytic degradation of the antigen. Depending on their fine specificity, they can "protect" well defined regions of the antigen. Because of steric hindrance between bound antibody and proteolytic enzyme, the protected region is larger than the minimal epitope recognized by the antibody binding site. The principle of limited proteolysis proves a valuable tool for the analysis of antigenic fragments and for epitope mapping. Since proteolysis of antigen also occurs in antigen presenting cells, degradation of antigen complexed with a monoclonal antibody (either taken up as an immunocomplex by Fc receptors, or taken up in complexed form with a surface immunoglobulin of a specific B cell) likely modulates the processing pattern of the antigen. This results in a different spectrum of peptides displayed by the antigen presenting cell and thus in different interactions with the antigen specific T cell repertoire. Modulation of T cell response and B cell response by using antigen complexed with different monoclonals is proposed as possible means of interfering with the fine specificity of the response.