T-cell based immunity is mediated through specific T cell receptor (TCR) recognition of a small antigenic peptide in complex with a host immune molecule, major histocompatibility complex (pMHC). The interaction of a TCR and its pMHC ligand is generally quite weak, degenerate and biophysically unfavorable. Yet, the resulting immune response is extremely effective, being both sensitive and specific.

Recent observations indicate that the TCR is an anisotropic mechanosensor. The force sensed by TCR’s recognition module is transmitted to the non-covalently associated signal transduction module. Multiple biophysical methods reveal that the molecular mechanism for TCR-pMHC interaction under force required to induce T cell signaling is linked to “catch bond” formation between a TCR and its cognate ligand pMHC. This kind of dynamic non-covalent bond actually increases the bond lifetime by deforming the molecule to make the interaction lock tighter. The key observation is that the more stimulatory the antigenic peptide, the more pronounced the catch bond and immune response. By contrast, an unrelated, non-antigenic peptide presented by the same MHC molecule does not form a catch bond, instead manifesting a slip bond associated with rapid TCR-pMHC dissociation. In summary, a weak interaction between a TCR and agonist ligand will be dramatically amplified by a catch bond under physical load generated by cell movement during immune surveillance.

These new biophysical concepts, TCR mechanosensor and dynamic catch bond formation, begin to reveal how bioforces tune T cell signaling and should be potentially enlightening for immunotherapy design against cancers.

基于T细胞的免疫是通过特异性T细胞受体（TCR）识别与宿主免疫分子（主要组织相容性复合物（pMHC））形成复合体的小抗原肽而介导的。TCR及其pMHC配体的相互作用通常非常弱，简并且在生物学上不利。然而，所产生的免疫反应是非常有效的，既敏感又特异性。

最近的观察表明，TCR是各向异性的机械传感器。由TCR的识别模块感测到的力被传输到非共价关联​​的信号转导模块。多种生物物理学方法表明，在诱导T细胞信号转导所需的力作用下，TCR-pMHC相互作用的分子机制与TCR及其同源配体pMHC之间的“捕获键”形成有关。这种动态的非共价键实际上是通过使分子变形以使相互作用锁定更紧密来延长键寿命的。关键观察结果是抗原肽刺激性越强，捕获键和免疫反应越明显。相比之下，同一MHC分子呈递的无关的非抗原肽不会形成捕获键，相反，它表现出与TCR-pMHC快速解离有关的滑键。总之，在免疫监视过程中，细胞运动产生的物理负荷下，TCR和激动剂配体之间的弱相互作用将被捕获键显着放大。

这些新的生物物理概念，即TCR机械传感器和动态捕获键的形成，开始揭示出生物力量如何调节T细胞信号传导，并有望为针对癌症的免疫疗法设计带来启发。