Antigen Decoding by T cells

描述（由申请人提供）：T细胞依赖于T细胞受体（TCR）触发的灵敏度、特异性和速度，以正确区分致病性和非致病性肽。T细胞如何将细胞外肽的空间和时间动力学因素化为适当的TCR触发和细胞活化还没有很好地理解，主要是因为该领域缺乏特异性操纵配体呈递给TCR的独立参数的工具。在以前的工作中，我们已经开发了光敏色素/PIF光可逆蛋白质-蛋白质相互作用模块，用于微米级的空间控制和第二级的时间控制。 胞内信号传导在这项研究中，我们正在调整这个模块的TCR信号光可逆激活。通过将这种光遗传学系统与TCR接合、TCR触发和细胞活化的测定相结合，我们将探索TCR配体如何被解码的基本问题。在全细胞水平上，我们正在研究配体呈递的空间和时间动力学对整体T细胞活化和极化的作用（目的1）。在分子水平上，我们正在研究配体动力学在触发TCR（Aim 2）中的作用。

DESCRIPTION (provided by applicant): T cells rely on the exquisite sensitivity, specificity, and speed of T cell receptor (TCR) triggering to properly distinguish pathogenic from non-pathogenic peptides. How T cells factor the spatial and temporal dynamics of extracellular peptides into appropriate TCR triggering and cellular activation is not well understood, largely because the field has lacked tools to specifically manipulate independent parameters of ligand presentation to the TCR. In previous work, we have developed the Phytochrome/PIF photoreversible protein-protein interaction module to for micron-level spatial control and second level temporal control of intracellular signaling. In this study, we are adapting this module for photoreversible activation f TCR signaling. By combining this optogenetic system with assays of TCR engagement, TCR triggering, and cellular activation, we will probe the fundamental question of how TCR ligands are decoded. On a whole-cell level, we are investigating the role of spatial and temporal dynamics of ligand presentation for overall T cell activation and polarization (Aim 1). On a molecular level, we are investigating the role of ligand kinetics in triggering the TCR (Aim 2).