This proposal is designed to investigate the process of antigen recognition by H-2 restricted cytotoxic T lymphocytes (CTL) and to examine pathways of antigen presentation in CTL recognition. A major related goal is to elucidate the relationship of H-2 restricted foreign antigen-specific CTL to the subset of alloreactive CTL. Our experimental approach is to use the type A influenza viruses as a model antigen for H-2 restricted CTL recognition and to examine the CTL response to this antigen at the clonal level. The recent advances in the cloning and long term in vitro cultivation of T lymphocytes now make it possible to characterize the specificity and functional activity of homogeneous CTL populations. We have concentrated our efforts on defining CTL specificity and now want to correlate CTL specificity at the clonal level with specific antigens and antigenic epitopes. Influenza virus is an extremely useful experimental system for this analysis because of the detailed information available on the structure and antigenicity of the virion constituents. This investigation will characterize at the molecular level antigenic epitopes recognized by cloned populations of H-2 restricted CTL and thereby provide a basis for defining sites of potential interaction between class I MHC gene products and foreign antigens. In addition, by elucidating pathways by which infectious and non-infectious forms of virus are presented to CTL, insight will be gained into the mechanisms of antigen presentation (and processing) to the CTL and its precursor. Our analysis on the relationship of MHC-restricted CTL to alloreactive CTL will focus on the extent of overlap between these two T cell subsets and the genetic and antigenic basis for this overlap. This work may provide insights into the mechanism of action of MHC-linked immune response genes.
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