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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
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T cell activation requires force generation.

Kenneth H Hu1, Manish J Butte2

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

The Journal of Cell Biology
|June 1, 2016
PubMed
Summary
This summary is machine-generated.

T cell activation involves both binding and mechanical forces. T cells use their cytoskeleton to generate forces, creating a feedback loop that enhances antigen recognition.

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Area of Science:

  • Immunology
  • Biophysics
  • Cell Biology

Background:

  • T cell receptor (TCR) triggering integrates binding kinetics and mechanical forces.
  • The T cell cytoskeleton's role in generating these forces remains incompletely understood.

Purpose of the Study:

  • To investigate the contribution of the T cell cytoskeleton to TCR-mediated mechanical forces.
  • To elucidate the interplay between mechanical forces and chemical signaling in T cell activation.

Main Methods:

  • Utilized atomic force microscopy (AFM) to apply controlled mechanical forces to T cells for antigenic stimulation.
  • Simultaneously employed optical microscopy for imaging and force measurements on the AFM cantilever.
  • Assessed the impact of F-actin inhibition on T cell force generation and calcium responses.

Main Results:

  • T cells exhibited forceful responses to antigen following calcium flux.
  • F-actin inhibition abrogated both force generation and calcium responses.
  • Exogenous forces applied via AFM could activate F-actin-inhibited T cells, but only when coupled through the TCR.
  • Purely mechanical stimulation without TCR coupling was insufficient for activation.

Conclusions:

  • TCR triggering involves a mechanical-chemical feedback loop.
  • T cell cytoskeleton generates forces essential for TCR-mediated activation.
  • Forceful T cell contacts enhance antigen access and recognition.