Spatiotemporal Patterning During T Cell Activation Is Highly Diverse

Sci. Signal., 7 April 2009
Vol. 2, Issue 65, p. ra15
DOI: 10.1126/scisignal.2000199

Spatiotemporal Patterning During T Cell Activation Is Highly Diverse

  1. Kentner L. Singleton1,*,
  2. Kole T. Roybal1,*,
  3. Yi Sun1,
  4. Guo Fu2,
  5. Nicholas R. J. Gascoigne2,
  6. Nicolai S. C. van Oers1, and
  7. Christoph Wülfing1,3,
  1. 1Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  2. 2Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  3. 3Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  1. To whom correspondence should be addressed. E-mail: christoph.wuelfing{at}utsouthwestern.edu
  • * These authors contributed equally to this work.

Abstract

Temporal and spatial variations in the concentrations of signaling intermediates in a living cell are important for signaling in complex networks because they modulate the probabilities that signaling intermediates will interact with each other. We have studied 30 signaling sensors, ranging from receptors to transcription factors, in the physiological activation of murine ex vivo T cells by antigen-presenting cells. Spatiotemporal patterning of these molecules was highly diverse and varied with specific T cell receptors and T cell activation conditions. The diversity and variability observed suggest that spatiotemporal patterning controls signaling interactions during T cell activation in a physiologically important and discriminating manner. In support of this, the effective clustering of a group of ligand-engaged receptors and signaling intermediates in a joint pattern consistently correlated with efficient T cell activation at the level of the whole cell.

Citation:

K. L. Singleton, K. T. Roybal, Y. Sun, G. Fu, N. R. Gascoigne, N. S. van Oers, and C. Wülfing, Spatiotemporal Patterning During T Cell Activation Is Highly Diverse. Sci. Signal. 2, ra15 (2009).

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O. Ksionda, A. Saveliev, R. Kochl, J. Rapley, M. Faroudi, J. E. Smith-Garvin, C. Wulfing, K. Rittinger, T. Carter, V. L. J. Tybulewicz et al.
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A. G. Ramsay, A. J. Clear, R. Fatah, and J. G. Gribben
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G. Fu, J. Hu, N. Niederberger-Magnenat, V. Rybakin, J. Casas, P. P. Yachi, S. Feldstein, B. Ma, J. A. H. Hoerter, J. Ampudia et al.
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