Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX37FY, United Kingdom.
Rosalind Franklin Institute, Harwell Campus, Didcot OX11 0FA, United Kingdom.
Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2404748121. doi: 10.1073/pnas.2404748121. Epub 2024 Sep 6.
Mechanical force has repeatedly been highlighted to be involved in T cell activation. However, the biological significance of mechanical force for T cell receptor signaling remains under active consideration. Here, guided by theoretical analysis, we provide a perspective on how mechanical forces between a T cell and an antigen-presenting cell can influence the bond of a single T cell receptor major histocompatibility complex during early T cell activation. We point out that the lifetime of T cell receptor bonds and thus the degree of their phosphorylation which is essential for T cell activation depends considerably on the T cell receptor rigidity and the average magnitude and frequency of an applied oscillatory force. Such forces could be, for example, produced by protrusions like microvilli during early T cell activation or invadosomes during full T cell activation. These features are suggestive of mechanical force being exploited by T cells to advance self-nonself discrimination in early T cell activation.
机械力在 T 细胞激活中被反复强调。然而，机械力对 T 细胞受体信号转导的生物学意义仍在积极研究中。在这里，我们在理论分析的指导下，提供了一个视角，说明 T 细胞和抗原呈递细胞之间的机械力如何影响早期 T 细胞激活过程中单个 T 细胞受体主要组织相容性复合物的结合。我们指出，T 细胞受体键的寿命，以及对 T 细胞激活至关重要的磷酸化程度，在很大程度上取决于 T 细胞受体的刚性和施加的振荡力的平均幅度和频率。这种力例如可以在早期 T 细胞激活期间由微绒毛等突起或完全 T 细胞激活期间的侵入小体产生。这些特征表明，机械力可被 T 细胞用于在早期 T 细胞激活中促进自身-非自身的区分。
