Our laboratory is currently investigating several immunological issues. Specifically, our research involves the analysis of the structural and functional relationships between peptide antigens and class II major histocompatibility molecules; requirements for peptide binding to class II molecules; T cell recognition of class II/peptide complexes; MHC transcriptional factors; and the mouse gamma-IFN receptor. The lab is also studying the immunological significance of tumor antigens, and the effects of the p53 nuclear protein on the proliferative phenotype of transformed cells. The proposed model of the class II molecule indicates that in the I-Ed peptide binding site a cluster of negatively charged residues may interact with the positive charged residues of the binding peptides. In antigen presenting cells, exogenous protein antigens, after their cellular processing, appear to associate only with newly synthesized class II molecules, whereas peptide antigens appear to occur on endocytosed cell surface class II molecules. During intractoplasmic recycling of MHC molecules a mechanism for peptide exchange has been identified. A naturally processed peptide derived from hen egg lysozyme has been identified as bound to purified class II molecules. The receptor for mouse interferon gamma has been cloned and will be used to analyze the signaling molecules involved in the biological activity of this molecule. We have structurally and functionally characterized the transformation-related p53 gene and its protein product. Transfection studies with wild type and mutant forms of the gene indicated the capability for both positive and negative control of proliferation by p53, specifically at the G1/S junction of the cell cycle. Another tumor antigen, previously identified as p82, has been cloned and identified as the murine homolog of cytovillin. Further analysis of the antigenic nature of HSP84/86 is in progress. The secondary and tertiary structure of IL-8 and two zinc peptides have been analyzed.
