Hu Kenneth H, Butte Manish J
Stanford Biophysics, Stanford University, Stanford, CA 94305.
Stanford Biophysics, Stanford University, Stanford, CA 94305 Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, Stanford University, Stanford, CA 94305
J Cell Biol. 2016 Jun 6;213(5):535-42. doi: 10.1083/jcb.201511053. Epub 2016 May 30.
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.
T细胞受体(TCR)的激活整合了结合动力学和机械力。为了解T细胞细胞骨架对这些力的作用,我们使用原子力显微镜(AFM)的一种新应用来激活T细胞。我们用AFM悬臂提供抗原刺激,同时用光学显微镜成像并测量悬臂上的力。钙流后,T细胞对抗原产生强烈反应。用F-肌动蛋白抑制剂处理后,所有的力和钙反应都被消除。当我们用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;外力必须通过TCR耦合。这些研究表明存在一种机械-化学反馈回路,其中TCR触发的T细胞与抗原呈递细胞产生有力接触,以改善对抗原的获取。