Monoclonal antibodies directed against the model protein antigen, lysozyme, c, are used as probes to study antibody-protein interactions and structure-function relationships, and to study developmentally regulated antigens in normal and neoplastic development. The interaction of antibodies with the epitopes are modeled and ultimately refined by protein cystallography studies. One antibody-lysozyme complex has been refined to 2.5 angstrom unit by X-ray cystallography. The results confirm the serologically predicted epitope and indicate a high degree of complementarity between the opposing surfaces. Another antibody-lysozyme complex has been studied in detail utilizing a new computer method for efficiently examining the interaction between 2 proteins. The conclusions from both studies are being tested with peptide binding experiments, by site-specific mutagenesis of in vitro expressed cloned immunoglobulin genes, and utilizing transgenic mice expressing the cloned lysozyme and/or antibody genes. The development of specificity for lysozyme from an apparently multispecific available antibody repertoire is currently being examined in detail utilizing large panels of hybridoma antibodies. In addition, monoclonal antibodies are being generated against bacterially expressed mouse c-myc protein; these antibodies will be used to purify and characterize structure-function relationships in the myc protein, applying the principles derived from the model protein studies.
