T cell activation requires force generation

Author:

Hu Kenneth H.1,Butte Manish J.12

Affiliation:

1. Stanford Biophysics, Stanford University, Stanford, CA 94305

2. Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, Stanford University, Stanford, CA 94305

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.

Funder

National Institutes of Health

National Institute of General Medicine Sciences

Children’s Health Research Institute

National Science Foundation

Publisher

Rockefeller University Press

Subject

Cell Biology

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