We propose to study the fine specificity of cytotoxic T cell recognition of influenza at the single cell level. Monoclonal T cells will be generated in short-term limiting dilution cultures and attempts will also be made to generate long-term cell lines with virus specificity. Initial work will focus on quantitating cytotoxic T cell precursors in the lymphoid organs of both immune and native mice, and on the determination of their specificity patterns using natural influenza variants, mutant viruses, and antibody-blocking protocols. The results of this work will provide a data base for the study of how the number and specificity of potentially responsive T cells is modified by manipulations of the immune system such as infection with other viruses, GvH and HvG responses, aging, and immunosuppression. In addition, analysis of cell-cell interactions in the generation and suppression of influenza-immune CTL, and of the recirculation chracteristics of these cells will be continued. Ontogenetic studies of the influenza-specific T cell repertoire will also be initiated. Cloned CTL populations will be used for analysis of T cell receptors both by assay on a variety of target cells which express different viral and MHC glycoproteins and in idiotypic studies.
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