This proposal is designed to investigate viral antigen recognition by H-2 restricted Cytolytic T Lymphocytes (CTL) and the process of viral antigen presentation in target cell sensitization for CIL recognition. It is a continuation of our ongoing study of the CIL response to type A influenza virus in the mouse. An important new direction in our research program has come from recent studies on a newly defined population of virus-specific CTL in the mouse. In addition to conventional CTL restricted in viral antigen recognition by class I (H-2K/D) major histocompatibility (MHC) locus products there is now good evidence for the existence of anti viral CTL restricted by class II (H-2I region) major histocompatibility locus products. The characterization of these class I MHC-restricted CTL as well as the continuing study of class II MHC restricted CTL is the focus of this research program. Our experimental approach will primarily employ clonal populations of H-2K/D and H-2I region restricted CTL: i) to define the influenza viral gene products which can serve as CTL target antigens; ii) to probe the molecular forms of viral antigen which can render target cells susceptible to lysis by CTL; iii) to map antigenic epitopes on the influenza hemagglutinin molecule recognized by CTL. Several eukaryotic expression vectors will be employed to get expression of influenza genes in various target cells and to get expression of truncated genes. This investigation should provide basic information on the immune response to an important human pathogen. Furthermore, these studies should help to elucidate the similarities and differences in the forms of viral antigens recognized by these two distinct CTL subsets and thereby provide a framework for future vaccine design.
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