Studies continue to focus on the role of cytotoxic T lymphocytes (CTL) in host immunity to viruses, using the murine response to type A influenza viruses as a model system. In previous work we have shown that recombinant vaccinia viruses containing cloned influenza virus genes can be used to both stimulate cytotoxic T lymphocytes (CTL) in vivo and in vitro, and to sensitize target cells for lysis by anti-influenza virus CTL. We found that contrary to expectations, a viral internal protein is recognized by anti-influenza CTL more efficiently than the major viral glycoprotein. Experiments will be continued at both population and clonal levels using vaccinia recombinants containing 7 influenza virus structural genes and 3 non-structural genes to further define the importance of individual virus gene products in the anti-influenza virus CTL response. We also propose to further study the role of CTL in modulating lethal and sublethal influenza pneumonia. The in vivo activities of CTL populations and cloned CTL cell lines will be correlated with their specificity for individual viral components and their production of gamma interferon. These studies will include an investigation of the immune mechanisms underlying our finding that immunization with recombinant vaccinia viruses protects mice against lethal influenza pneumonia. Finally, we propose to study the influence of the major histocompatibility complex in the recognition of individual viral components. This will include determining the class I MHC restruction elements for each of the viral components recognized as well as an examination of the phenomenon of MHC associated CTL low responsiveness to influenza virus.