Our research invloves the molecular structure of histocompatibility antigens, T cell helper and suppressor receptors and tumor antigens using a combination of protein and DNA sequencing in conjunction with peptide and nucleotide synthesis. Recombinant DNA constructs were used to elucidate the contribution of individual amino acids as well as of the individual alpha 1/ alpha 2 domains of class I antigens toward allo and H-2 restricted CTL reactivity. We have identified three distinct factors in nuclear extracts which binds discrete sequences within the H-2 class I regulator element. Our data also indicate that in the interferonconsensus sequence of class I genes, a 10 bp site binds both constitutive and inducible factors. One of the tumor specific transplantation antigens of the Meth A tumor has been shown to consist of two protein isoforms identified as being the 90 kDa heat shock proteins (hsp). The DNA sequence of these two hsp from Meth A has been completed and that of their normal counterparts is currently being pursued. Chromosomal assignment and localization of one isoform has been found to be near the MHC locus on chromosome 17. Complete sequence analysis of these antigens and their normal counterparts should permit identification of the molecular changes which elicit cell mediated immunity. DNA sequences predicted to have aberrant helices d(CGCAGAATTCGCG) and d(CGCGAAATTTACGCG) have been crystallized. These sequences showed an overall B-type conformation with two unpaired adenosines looped out from the double helix. These structures are important for defining mechanisms of mutations.
