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Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist.

Publication ,  Journal Article
Huse, M; Klein, LO; Girvin, AT; Faraj, JM; Li, Q-J; Kuhns, MS; Davis, MM
Published in: Immunity
July 2007

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.

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Published In

Immunity

DOI

ISSN

1074-7613

Publication Date

July 2007

Volume

27

Issue

1

Start / End Page

76 / 88

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell
  • Photoaffinity Labels
  • Peptides
  • Nitrobenzenes
  • Moths
  • Molecular Sequence Data
  • Mice
  • Lymphocyte Activation
 

Citation

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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
Huse, Morgan, Lawrence O. Klein, Andrew T. Girvin, Joycelyn M. Faraj, Qi-Jing Li, Michael S. Kuhns, and Mark M. Davis. “Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist.Immunity 27, no. 1 (July 2007): 76–88. https://doi.org/10.1016/j.immuni.2007.05.017.
Huse M, Klein LO, Girvin AT, Faraj JM, Li Q-J, Kuhns MS, et al. Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist. Immunity. 2007 Jul;27(1):76–88.
Huse, Morgan, et al. “Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist.Immunity, vol. 27, no. 1, July 2007, pp. 76–88. Pubmed, doi:10.1016/j.immuni.2007.05.017.
Huse M, Klein LO, Girvin AT, Faraj JM, Li Q-J, Kuhns MS, Davis MM. Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist. Immunity. 2007 Jul;27(1):76–88.
Journal cover image

Published In

Immunity

DOI

ISSN

1074-7613

Publication Date

July 2007

Volume

27

Issue

1

Start / End Page

76 / 88

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell
  • Photoaffinity Labels
  • Peptides
  • Nitrobenzenes
  • Moths
  • Molecular Sequence Data
  • Mice
  • Lymphocyte Activation