Institute of Applied Physics, TU Wien, Vienna, Austria.
Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Medical University of Vienna, Vienna, Austria.
Nat Immunol. 2018 May;19(5):487-496. doi: 10.1038/s41590-018-0092-4. Epub 2018 Apr 16.
T cell antigen recognition requires T cell antigen receptors (TCRs) engaging MHC-embedded antigenic peptides (pMHCs) within the contact region of a T cell with its conjugated antigen-presenting cell. Despite micromolar TCR:pMHC affinities, T cells respond to even a single antigenic pMHC, and higher-order TCRs have been postulated to maintain high antigen sensitivity and trigger signaling. We interrogated the stoichiometry of TCRs and their associated CD3 subunits on the surface of living T cells through single-molecule brightness and single-molecule coincidence analysis, photon-antibunching-based fluorescence correlation spectroscopy and Förster resonance energy transfer measurements. We found exclusively monomeric TCR-CD3 complexes driving the recognition of antigenic pMHCs, which underscores the exceptional capacity of single TCR-CD3 complexes to elicit robust intracellular signaling.
T 细胞抗原识别需要 T 细胞抗原受体（TCRs）与 T 细胞与其共轭抗原呈递细胞的接触区域内的 MHC 嵌入的抗原肽（pMHC）结合。尽管 TCR：pMHC 的亲和力为微摩尔级，但 T 细胞即使对单个抗原性 pMHC 也有反应，并且已经假定更高阶的 TCR 可以维持高抗原敏感性并触发信号转导。我们通过单分子亮度和单分子符合分析、基于光子聚束的荧光相关光谱法和Förster 共振能量转移测量，研究了活 T 细胞表面 TCR 和其相关 CD3 亚基的计量比。我们发现仅单体 TCR-CD3 复合物可驱动抗原性 pMHC 的识别，这突显了单个 TCR-CD3 复合物引发强大细胞内信号转导的非凡能力。
