The cytotoxic T lymphocyte (CTL) plays an important role in graft rejection and antiviral protection. In addition, these cells provide a unique model for studies of cell-cell interaction and induction of cellular function. When the CTL or its progenitor encounters a cell expressing on its surface an antigen for which the CTL has a receptor, a number of consequences can ensue: 1) an immature or memory CTL can initiate a series of events leading to its functional maturation; 2) a fully differentiated CTL can initiate target cell lysis; 3) both mature and immature cells can initiate the series of events leading to cell division; 4) mature cells (immature cells?) release lymphokines. We have developed clonal models that will allow us to begin to dissect the components of each of these functional responses. Coupled to our understanding of the nature of these various functional components will be studies characterizing the immune signals regulating their expression. Finally, we will begin a series of experiments designed to take advantage of unique characteristics of our clones that may allow us to select for a series of mutant CTL that have defects in their functional machinery. Use of these mutant cells in standard somatic cell genetic experiments will allow us to begin to address the interaction between the individual components required to transmit the signal from receptor binding to the expression of biological function.
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