This proposal entails the study of the antigenic requirements for triggering of cytolytic T lymphocytes (CTLs) and the cell interactions that regulate this response. Specifically, this study includes the isolation and characterization of protein antigens from influenza virus, from uninfected murine cells, and from influenza virus-infected murine cells. These proteins will be inserted into phospholipid vesicles (liposomes) and used to define the antigenic requirements for the elicitation of immune responses by murine T lymphocytes in vitro. The responses to be studied are the generation of influenza virus-specific CTLs (i.e., these cells kill virus-infected, major histocompatibility antigen identical cells) and helper T cells (i.e., these cells augment the cytolytic activity of CTLs and may produce helper factors). Cell lines which respond to influenza virus antigens will be established and cloned and their response to purified viral and cell surface antigens will be studied. The cell interactions between different functional subsets of lymphocytes which regulate the CTL response to influenza virus will also be evaluated. Among these cell types are helpers, amplifier cells, suppressor cells, and precursors of cytolytic cells. It is hoped that the understandings which develop from these studies can be applied to the human response to influenza virus, which causes epidemic disease, and later to understanding the immune response to cancer. Once we understand the antigens recognized by CTLs and the cell interactions that regulate this immune response, we may begin to intervene in order to modulate the host's response to viral infections and malignancies.
