Spatial and Temporal Dynamics of T Cell Receptor Signaling with a Photoactivatable Agonist

Morgan Huse, Lawrence O. Klein, Andrew T. Girvin, Joycelyn M. Faraj, Qi Jing Li, Michael S. Kuhns, Mark M. Davis

Research output: Contribution to journalArticle

162 Scopus citations

Abstract

The precise timing of signals downstream of the T cell receptor (TCR) is poorly understood. To address this problem, we prepared major histocompatibility complexes containing an antigenic peptide that is biologically inert until exposed to ultraviolet (UV) light. UV irradiation of these complexes in contact with cognate T cells enabled the high-resolution temporal analysis of signaling. Phosphorylation of the LAT adaptor molecule was observed in 4 s, and diacylglycerol production and calcium flux was observed in 6-7 s. TCR activation also induced cytoskeletal polarization within 2 min. Antibody blockade of CD4 reduced the intensity of LAT phosphorylation and the speed of calcium flux. Furthermore, strong desensitization of diacylglycerol production, but not LAT phosphorylation, occurred shortly after TCR activation, suggesting that different molecular events play distinct signal-processing roles. These results establish the speed and localization of early signaling steps, and have important implications regarding the overall structure of the network.

Original languageEnglish (US)
Pages (from-to)76-88
Number of pages13
JournalImmunity
Volume27
Issue number1
DOIs
StatePublished - Jul 27 2007

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Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Huse, M., Klein, L. O., Girvin, A. T., Faraj, J. M., Li, Q. J., Kuhns, M. S., & Davis, M. M. (2007). Spatial and Temporal Dynamics of T Cell Receptor Signaling with a Photoactivatable Agonist. Immunity, 27(1), 76-88. https://doi.org/10.1016/j.immuni.2007.05.017