The major area of our research involves the molecular structure of histocompatibility antigens, T cell suppressor receptors and tumor antigens using a combination of protein and DNA sequencing in conjunction with peptide and nucleotide synthesis. Oligonucleotide directed site mutagenesis and recombinant DNA constructs have been employed to elucidate the role of individual amino acids as well as of the individual domains on the function and expression of class I histocompatibility antigens. A cDNA library from a rearranged T cell suppressor clone specific for lysozyme has been generated and Alpha and Beta T cell receptor clones have been isolated. These clones will enable us to investigate the role of these genes in the mechanism of T cell suppression. A tumor specific transplantation antigen from a methylcholanthrene-induced tumor has been identified as a heat shock protein by partial amino acid and DNA sequence analysis. Further analysis should permit identification of the molecular change in this antigen which elicit cell mediated immunity. DNA sequences predicted to have aberrant helices with inserted bases, forming hairpin stem and loops, have been crystallized. These structures may serve as a model indicating why certain sequences have a much greater tendency to mutate than others and how proteins recognize particular regions of DNA.
