Antigen Decoding by T cells

T 细胞解码抗原

基本信息

批准号：
8668697
负责人：
Morgan A Huse
金额：
$ 29.16万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/8668697
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 Individual Invaded Kinetics Life Ligand Binding Ligands Location Measurement Measures Methods Microtubule-Organizing Center Microtubules Modeling Molecular Monitor Pattern Peptides Phytochrome Play Point Mutation Positioning Attribute Property Receptor Activation Receptor Signaling Role 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 biophysical properties cytokine cytotoxic extracellular immunological synapse immunological synapse formation optogenetics pathogen protein protein interaction public health relevance receptor research study response spatial integration tool two-dimensional vaccine development

项目摘要

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 细胞依靠 T 细胞受体 (TCR) 触发的精确灵敏度、特异性和速度来正确区分致病性和非致病性肽。 T 细胞如何将胞外肽的空间和时间动态分解为适当的 TCR 触发和细胞激活尚不清楚，很大程度上是因为该领域缺乏专门操纵 TCR 配体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光可逆蛋白质-蛋白质相互作用模块，用于微米级空间控制和二级时间控制细胞内信号传导。在这项研究中，我们正在调整该模块以实现 TCR 信号传导的光可逆激活。通过将该光遗传学系统与 TCR 结合、TCR 触发和细胞激活分析相结合，我们将探讨 TCR 配体如何解码的基本问题。在全细胞水平上，我们正在研究配体呈递的空间和时间动态对整体 T 细胞激活和极化的作用（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）。