Chromatin remodelling and transcriptional regulation of CD8 T cell effector gene expression

细胞毒性T细胞或杀伤T细胞的主要作用是从宿主中识别和去除病毒感染的细胞或肿瘤细胞。在识别靶宿主细胞后，杀伤性T细胞递送称为颗粒酶的蛋白质包，其介导这些病毒感染和肿瘤细胞的去除。初始杀伤T细胞需要被激活以开始产生这些效应分子。该建议计划检查调节这些效应分子的细胞特异性表达的诱导和维持的因素。我们计划确定细胞基因组中发生的分子事件，以打开颗粒酶基因表达，以及这些因素如何影响随后的杀伤T细胞功能。这些研究的结论将使我们能够确定为什么一些杀伤T细胞反应是无效的，以及可以做些什么来改善杀伤T细胞功能。这对开发旨在诱导针对病毒和肿瘤挑战的免疫力的新型疫苗策略具有影响。

A major role for cytotoxic, or killer, T cells is the recognition and removal of virus infected or tumor cells from a host. Upon recognition of a target host cell, killer T cells deliver a package of proteins, termed granzymes, that mediate the removal of these virus infected and tumor cells. Naive killer T cells need to be activated to start producing these effector molecules. This proposal plans to examine the factors that regulate both induction and maintanence of cell specific expression of these effector molecules. We plan to identify the molecular events that occur within a cells genome to turn on granzyme gene expression and how these factors influence subsequent killer T cell function. The conclusions from these studies will enable us to determine why some killer T cell responses are not effective and what can be done to improve killer T cell function. This has implications for the development of novel vaccine strategies designed to induce immunity against both viral and tumour challenges.