单体 TCR 驱动 T 细胞抗原识别。
Monomeric TCRs drive T cell antigen recognition.
机构信息
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.
出版信息
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。
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