Feedback control of T-cell receptor activation

Proc Biol Sci. 2004 May 7;271(1542):931-9. doi: 10.1098/rspb.2003.2587.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Feedback, Physiological / immunology*
  • Ligands
  • Models, Immunological*
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphotransferases / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Sensitivity and Specificity
  • Signal Transduction / immunology*
  • Stochastic Processes

Substances

  • Ligands
  • Receptors, Antigen, T-Cell
  • Phosphotransferases
  • Phosphoric Monoester Hydrolases