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

T细胞抗原敏感性受T细胞受体（TCR）和肽/MHC（pMHC）接合后传递的信号传导事件调节，这是引发各种效应子功能所需的。抗原特异性T细胞活性的表型差异是经常观察到的，然而，精确的细胞和分子的细节，调节这一过程还没有得到充分的表征。 本研究项目的目的是使用一种强大且高度灵活的报告T细胞系统来研究TCR生物学和TCR介导的信号传导事件。将使用一组充分表征的TCR来检查TCR序列和pMHC结合动力学对信号强度的影响。将表征天然存在的TCR库内抗原特异性TCR序列和功能的多样性。最后，将评估已知的共调节蛋白和改变的膜动力学对TCR功能的影响。 这些研究的结果将大大推进我们对T细胞生物学的理解，包括调节TCR功能和信号传导活性的细胞和分子机制。这项工作的结果预计将特别感兴趣的研究人员在细胞免疫学和信号转导领域的工作。

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.