Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN.
The Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN.
J Immunol. 2023 Aug 1;211(3):325-332. doi: 10.4049/jimmunol.2300121.
Recognition of peptide/MHC complexes by αβ TCRs has traditionally been viewed through the lens of conventional receptor-ligand theory. Recent work, however, has shown that TCR recognition and T cell signaling can be profoundly influenced and tuned by mechanical forces. One outcome of applied force is the catch bond, where TCR dissociation rates decrease (half-lives increase) when limited force is applied. Although catch bond behavior is believed to be widespread in biology, its counterintuitive nature coupled with the difficulties of describing mechanisms at the structural level have resulted in considerable mystique. In this review, we demonstrate that viewing catch bonds through the lens of energy landscapes, barriers, and the ensuing reaction rates can help demystify catch bonding and provide a foundation on which atomic-level TCR catch bond mechanisms can be built.
αβ TCR 识别肽/MHC 复合物的传统观点是基于传统的受体-配体理论。然而，最近的研究表明，TCR 识别和 T 细胞信号转导可以受到机械力的深刻影响和调节。施加力的一个结果是捕获键，当施加有限的力时，TCR 解离速率会降低（半衰期增加）。尽管捕获键行为被认为在生物学中很普遍，但由于其反直觉的性质以及在结构水平上描述机制的困难，导致其具有相当大的神秘感。在这篇综述中，我们证明通过能量景观、障碍以及由此产生的反应速率的视角来看待捕获键，可以帮助揭开捕获键的神秘面纱，并为构建原子水平 TCR 捕获键机制提供基础。
