Characterization of signalling mechanisms that regulate antigen sensitivity and cytotoxic functions in CD8+ T lymphocytes

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T cell antigen sensitivity is regulated by the T cell receptor (TCR) and by signalling events transmitted following peptide/MHC (pMHC) engagement, which are required to elicit various effector functions. Phenotypic differences in antigen-specific T cell activity are frequently observed; however, the precise cellular and molecular details that regulate this process have not been fully characterized. The objective of this research program is to investigate TCR biology and TCR-mediated signalling events using a robust and highly flexible reporter T cell system. The impact of TCR sequence and pMHC binding kinetics on signalling strength will be examined using a panel of well characterized TCRs. The diversity of antigen-specific TCR sequence and function within a naturally occurring TCR repertoire will be characterized. Finally, the impact of known co-regulatory proteins and altered membrane dynamics on TCR function will be assessed. The results of these studies will significantly advance our understanding of T cell biology, including the cellular and molecular mechanisms that regulate TCR function and signalling activity. The outcome of this work is expected to be of particular interest to researcher working in the fields of cellular immunology and signal transduction.