Antigen Decoding by T cells

描述（由申请人提供）：T细胞依靠T细胞受体（TCR）触发的敏感性、特异性和速度来正确区分致病性和非致病性肽。T细胞如何将细胞外肽的时空动态因子转化为适当的TCR触发和细胞激活尚不清楚，主要是因为该领域缺乏专门操纵配体向TCR呈递的独立参数的工具。在之前的工作中，我们开发了光敏色素/PIF光可逆蛋白-蛋白相互作用模块，用于微米级空间控制和二级时间控制

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).