To eliminate antigens that are recognized as nonself (foreign) the immune system uses many strategies, including antibodies and complement, activated macrophages, and T lymphocytes having cytotoxic activity. Our goal is to understand cytotoxic T lymphocytes (Tc cells), particularly their recognition of antigens in the restricted contest of autologous (self) histocompatibility (H) antigens and their activation of cytotoxic molecules and processes, which are triggered when these cytotoxic cells recognize target cells bearing the appropriate antigen (and H proteins). To understand antigen recognition we will compare the immunoglobullin (Ig)-like T cell receptor Alpah, Beta, and Gamma genes that are expressed in both mature Tc cells and in immature thymocytes, comparing especially V and V-J joining region sequences of receptors from cells of the three congenic BALB strains (BALB/c [H-2d], BALB.B [H-2b], and BALB.K [H-2k]). The comparison should reveal whether H antigens in the environment of developing T cells influences the V domains of the Alpha, Beta, and Gamma V chains and J that are expressed in mature Tc cells. The product and function of the Ig-like T cell Gamma Y gene are still enigmatic and special efforts will be made to identify the Gamma chain, focussing on the liklihood that it is a phosphorylated subunit of a membrane-associated, dimeric protein. Purified, soluble human H antigens will also be used to establish the intrinsic affinity of T cell receptors on cloned human Tc cell lines that are specific for these H antigens, some of which have a well-characterized 3-dimensional structure. T analyze some molecules involved in cytolysis of target cells, the properties of a novel esterase recentlly described in murine Tc cells will be analyzed and the gene encoding this enzyme will be studied to determine the extent of its homology, if any, to complement proteins. Finnally, heterobifunctional (""""""""duplex"""""""") antibodies will be studied to determine their effectiveness in targeting any selected cell for destruction by Tc cells, regardless of the latter's antigen-specificity.
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