Antigen Decoding by T cells

T 细胞解码抗原

• 批准号: 9222774
• 负责人: Morgan A Huse
• 金额: $ 31.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-05 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9222774
• 关键词: Address; Affect; Affinity; Agonist; Antigens; Area; Autoimmune Diseases; Biological Assay; Cell division; Cells; Confounding Factors (Epidemiology); Coupled; Cytoskeleton; Data; Detection; Dissociation; Emerging Technologies; Immune response; Immune system; Income; Individual; Invaded; Kinetics; Ligand Binding; Ligands; Location; Measurement; Measures; Methods; Microtubule-Organizing Center; Microtubules; Modeling; Molecular; Monitor; Pathogenicity; Pattern; Peptides; Phytochrome; Play; Point Mutation; Positioning Attribute; Property; Receptor Activation; Receptor Signaling; Role; Secretory Cell; Sensitivity and Specificity; Signal Transduction; Spatial Distribution; Specificity; Speed; System; T memory cell; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; TCF Transcription Factor; Testing; Time; Translating; Variant; Work; adaptive immune response; biophysical properties; cytokine; cytotoxic; experimental study; extracellular; immunological synapse; immunological synapse formation; optogenetics; pathogen; polarized cell; protein protein interaction; public health relevance; receptor; response; spatial integration; tool; two-dimensional; vaccine development

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).

描述(由申请人提供)：T细胞依赖于T细胞受体(TCR)触发的高度敏感性、特异性和速度来正确区分致病多肽和非致病多肽。T细胞如何将细胞外肽的空间和时间动力学因素引入适当的TCR触发和细胞激活尚不清楚，这主要是因为该领域缺乏工具来具体操作向TCR呈递配体的独立参数。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二级的时间控制。 细胞内信号。在这项研究中，我们正在调整该模块以用于TCR信号的光可逆激活。通过将这个光遗传系统与TCR参与、TCR触发和细胞激活的分析相结合，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在总体T细胞激活和极化中的作用(目标1)。在分子水平上，我们正在研究配体动力学在触发TCR中的作用(目标2)。