T cell activation requires force generation.
T cell activation requires force generation.
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DOI：
10.1083/jcb.201511053
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发表时间：
2016-06-06
期刊：
影响因子：
--
通讯作者：
Butte MJ
中科院分区：
文献类型：
--
作者：
Hu KH;Butte MJ
T细胞受体需要力来触发。在这里，胡和布特表明，T细胞产生推力和拉力对抗原涂层的原子力显微镜悬臂在肌动蛋白依赖的方式。在没有完整的F-肌动蛋白细胞骨架的情况下，由悬臂提供的外源性振荡力拯救了T细胞受体信号传导。这些发现强调了机械力在T细胞活化中的重要性。T细胞受体（TCR）的触发整合了结合动力学和机械力。为了了解T细胞细胞骨架对这些力的贡献，我们使用原子力显微镜（AFM）的新应用触发了T细胞。我们提出了抗原刺激使用AFM悬臂，同时与光学显微镜成像和测量力的悬臂。T细胞在钙流后对抗原有强有力的反应。所有的力量和钙反应废除后，用F-肌动蛋白抑制剂治疗。当我们使用AFM悬臂模拟T细胞的力时，即使是这些肌动蛋白抑制的T细胞也被激活了。单纯的机械刺激是不够的;外源性力必须通过TCR偶联。这些研究表明，TCR触发的T细胞与抗原呈递细胞产生强有力的接触，以改善对抗原的获取，这是一个机械-化学反馈回路。
The T cell receptor requires force for triggering. Here, Hu and Butte show that T cells generate pushing and pulling forces against an antigen-coated AFM cantilever in an actin-dependent fashion. Exogenous, oscillating forces delivered by the cantilever rescued T cell receptor signaling in the absence of an intact F-actin cytoskeleton. These findings highlight the importance of mechanical forces in T cell activation. Triggering of the T cell receptor (TCR) integrates both binding kinetics and mechanical forces. To understand the contribution of the T cell cytoskeleton to these forces, we triggered T cells using a novel application of atomic force microscopy (AFM). We presented antigenic stimulation using the AFM cantilever while simultaneously imaging with optical microscopy and measuring forces on the cantilever. T cells respond forcefully to antigen after calcium flux. All forces and calcium responses were abrogated upon treatment with an F-actin inhibitor. When we emulated the forces of the T cell using the AFM cantilever, even these actin-inhibited T cells became activated. Purely mechanical stimulation was not sufficient; the exogenous forces had to couple through the TCR. These studies suggest a mechanical–chemical feedback loop in which TCR-triggered T cells generate forceful contacts with antigen-presenting cells to improve access to antigen.