Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Department of Translational Medicine, Sidra Medicine, Doha, Qatar.
Commun Biol. 2022 Jan 11;5(1):40. doi: 10.1038/s42003-021-02995-1.
T cells are critically important for host defense against infections. T cell activation is specific because signal initiation requires T cell receptor (TCR) recognition of foreign antigen peptides presented by major histocompatibility complexes (pMHC) on antigen presenting cells (APCs). Recent advances reveal that the TCR acts as a mechanoreceptor, but it remains unclear how pMHC/TCR engagement generates mechanical forces that are converted to intracellular signals. Here we propose a TCR Bending Mechanosignal (TBM) model, in which local bending of the T cell membrane on the nanometer scale allows sustained contact of relatively small pMHC/TCR complexes interspersed among large surface receptors and adhesion molecules on the opposing surfaces of T cells and APCs. Localized T cell membrane bending is suggested to increase accessibility of TCR signaling domains to phosphorylation, facilitate selective recognition of agonists that form catch bonds, and reduce noise signals associated with slip bonds.
T 细胞对于宿主抗感染防御至关重要。T 细胞的激活具有特异性，因为信号的起始需要 T 细胞受体（TCR）识别主要组织相容性复合物（MHC）上呈递的外来抗原肽（pMHC）在抗原呈递细胞（APC）上。最近的研究进展表明，TCR 作为一种机械感受器，但其尚不清楚 pMHC/TCR 结合如何产生机械力，这些力被转化为细胞内信号。在这里，我们提出了一个 TCR 弯曲机械信号（TBM）模型，该模型表明，T 细胞膜在纳米尺度上的局部弯曲允许相对较小的 pMHC/TCR 复合物与 T 细胞和 APC 相对表面上的大表面受体和粘附分子之间的持续接触。局部化的 T 细胞膜弯曲被认为可以增加 TCR 信号结构域的磷酸化可及性，促进形成捕获键的激动剂的选择性识别，并减少与滑键相关的噪声信号。
