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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Huse, M; Klein, LO; Girvin, AT; Faraj, JM; Li, Q-J; Kuhns, MS; Davis, MM

Published Date

  • July 2007

Published In

Volume / Issue

  • 27 / 1

Start / End Page

  • 76 - 88

PubMed ID

  • 17629516

Pubmed Central ID

  • 17629516

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2007.05.017

Language

  • eng

Conference Location

  • United States