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单价T细胞抗原受体复合物驱动T细胞抗原识别

Monovalent T-cell antigen receptor complexes drive T-cell antigen recognition
课程网址: http://videolectures.net/biophysics2018_brameshuber_antigen_recog...  
主讲教师: Mario Brameshuber
开课单位: 应用物理研究所
开课时间: 2018-07-09
课程语种: 英语
中文简介:
T细胞通过其克隆型T细胞抗原受体(TCR)识别抗原呈递细胞(APC)上的MHC嵌入抗原肽片段(PMCC),TCR通常对其pMHC配体具有中等亲和力。高阶TCR结构,无论是组成性存在还是在pMHC结合时动态形成,长期以来一直被认为是细胞内T细胞信号传导和维持高抗原敏感性的工具。在这里,我们使用(i)光漂白后单分子荧光恢复,(ii)Förster共振能量转移(FRET)和(iii)测定了活抗原体验T细胞中TCR及其非共价相关CD3信号链的化学计量比基于光子到达时间的荧光相关光谱(FCS)测量。使用这些方法,我们在pMHC绑定之前和绑定期间发现了唯一的单体TCR实体。因此,TCR聚集以外的分子事件在高密度和低密度下驱动pMHCs的识别。
课程简介: T-cells recognize MHC-embedded antigenic peptide fragments (pMHCs) on antigen presenting cells (APCs) through their clonotypic T-cell antigen receptors (TCRs), which typically feature only moderate affinities towards their pMHC ligands. Higher order TCR-structures, either constitutively present or dynamically formed upon pMHC binding, have thus long been considered instrumental for intracellular T-cell signaling and for maintaining high antigen sensitivity. Here we have determined the stoichiometry of the TCR and their non-covalently associated CD3 signaling chains in living antigen-experienced T-cells with the use of (i) single molecule Fluorescence Recovery After Photobleaching, (ii) Förster Resonance Energy Transfer (FRET) and (iii) photon arrival time - based fluorescence correlation spectroscopy (FCS) measurements. Using these approaches, we find exclusively monomeric TCR entities prior to and during pMHC binding. Hence, molecular events other than TCR clustering drive the recognition pMHCs at both high and low densities.
关 键 词: T细胞; 单体TCR实体; 克隆型T细胞
课程来源: 视频讲座网
数据采集: 2021-11-12:zkj
最后编审: 2021-11-12:zkj
阅读次数: 39