The goals of this group are to identify the structure and the regulated expression of the T cell antigen receptor complex. In addition, an important component to the work of this group is to utilize mutants combined with recombinant DNA technology to begin to establish structure/function relations for this important immunologic receptor. The structure of two different receptor complexes on the surface of T cells have been defined. Both complexes contain the alpha and beta heterodimeric antigen recognition structures non-covalently coupled to the three membered CD3 complex. The two classes of receptors are distinguished by their containing either a zeta-zeta homodimeric structure or a zeta-eta heterodimeric structure in addition to these five other components. This group has used gene transfection studies to try to address the subunit interactions within the receptor complex. In addition, this group has focused on the zeta and eta chains of the TCR complex, both in terms of the molecular biology, the biochemistry, the assembly and structure/function relations. Eta deficient variants have been isolated and characterized, as well as zeta negative variants and mutants. The eta chain has been biochemically characterized and its immunologic relationship to zeta identified. The zeta chain is transcriptionally regulated in a very intriguing way, and this has been correlated with structural changes in the gene. The full structure of the gene has been identified. The structure of zeta has been altered by site-directed mutagenesis and this has been utilized to reconstruct the first signal transduction mutants of the TCR complex.
