Feedback control of T-cell receptor activation.

Journal Article

The specificity and sensitivity of T-cell recognition is vital to the immune response. Ligand engagement with the T-cell receptor (TCR) results in the activation of a complex sequence of signalling events, both on the cell membrane and intracellularly. Feedback is an integral part of these signalling pathways, yet is often ignored in standard accounts of T-cell signalling. Here we show, using a mathematical model, that these feedback loops can explain the ability of the TCR to discriminate between ligands with high specificity and sensitivity, as well as provide a mechanism for sustained signalling. The model also explains the recent counter-intuitive observation that endogenous 'null' ligands can significantly enhance T-cell signalling. Finally, the model may provide an archetype for receptor switching based on kinase-phosphatase switches, and thus be of interest to the wider signalling community.

Full Text

Duke Authors

Cited Authors

  • Chan, C; Stark, J; George, AJT

Published Date

  • May 7, 2004

Published In

Volume / Issue

  • 271 / 1542

Start / End Page

  • 931 - 939

PubMed ID

  • 15255048

International Standard Serial Number (ISSN)

  • 0962-8452

Digital Object Identifier (DOI)

  • 10.1098/rspb.2003.2587

Language

  • eng

Conference Location

  • England