Mechanisms of localized activation of the T cell antigen receptor inside clusters

Yair Neve-Oz, Yair Razvag, Julia Sajman, Eilon Sherman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The T cell antigen receptor (TCR) has been shown to cluster both before and upon engagement with cognate antigens. However, the effect of TCR clustering on its activation remains poorly understood. Here, we used two-color photo-activated localization microscopy (PALM) to visualize individual molecules of TCR and ZAP-70, as a marker of TCR activation and phosphorylation, at the plasma membrane of uniformly activated T cells. Imaging and second-order statistics revealed that ZAP-70 recruitment and TCR activation localized inside TCR clusters. Live cell PALM imaging showed that the extent of localized TCR activation decreased, yet remained significant, with cell spreading. Using dynamic modeling and Monte-Carlo simulations we evaluated possible mechanisms of localized TCR activation. Our simulations indicate that localized TCR activation is the result of long-range cooperative interactions between activated TCRs, or localized activation by Lck and Fyn. Our results demonstrate the role of molecular clustering in cell signaling and activation, and are relevant to studying a wide range of multi-molecular complexes. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.

Original languageAmerican English
Pages (from-to)810-821
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number4
DOIs
StatePublished - 1 Apr 2015

Bibliographical note

Publisher Copyright:
© 2014 Elsevier B.V.

Keywords

  • Immune synapse
  • Microcluster
  • Modeling and simulation
  • Nanocluster
  • Photoactivated localization microscopy
  • Super-resolution light microscopy
  • T cell activation
  • T cell receptor

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