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T细胞活化需要产生力。

T cell activation requires force generation.

作者信息

Hu Kenneth H, Butte Manish J

机构信息

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

出版信息

J Cell Biol. 2016 Jun 6;213(5):535-42. doi: 10.1083/jcb.201511053. Epub 2016 May 30.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae26/4896056/eb2b99d56410/JCB_201511053_Fig1.jpg

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本文引用的文献

1
Actin depletion initiates events leading to granule secretion at the immunological synapse.
Immunity. 2015 May 19;42(5):864-76. doi: 10.1016/j.immuni.2015.04.013.
2
Early T cell activation: integrating biochemical, structural, and biophysical cues.
Annu Rev Immunol. 2015;33:539-61. doi: 10.1146/annurev-immunol-032414-112158.
3
Advanced methods of microscope control using μManager software.
J Biol Methods. 2014;1(2). doi: 10.14440/jbm.2014.36.
4
Force-dependent transition in the T-cell receptor β-subunit allosterically regulates peptide discrimination and pMHC bond lifetime.
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1517-22. doi: 10.1073/pnas.1424829112. Epub 2015 Jan 20.
6
Spatiotemporally and mechanically controlled triggering of mast cells using atomic force microscopy.
Immunol Res. 2014 May;58(2-3):211-7. doi: 10.1007/s12026-014-8510-7.
7
Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling.
Cell. 2014 Apr 10;157(2):357-368. doi: 10.1016/j.cell.2014.02.053.
8
The transcription factor NFAT exhibits signal memory during serial T cell interactions with antigen-presenting cells.
Immunity. 2013 Feb 21;38(2):237-49. doi: 10.1016/j.immuni.2012.09.012. Epub 2013 Jan 11.
9
Biophysical mechanism of T-cell receptor triggering in a reconstituted system.
Nature. 2012 Jul 5;487(7405):64-9. doi: 10.1038/nature11220.
10
Antigen recognition is facilitated by invadosome-like protrusions formed by memory/effector T cells.
J Immunol. 2012 Apr 15;188(8):3686-99. doi: 10.4049/jimmunol.1102594. Epub 2012 Mar 21.

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