Feedback control of T–cell receptor activation

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 signallin...

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Bibliographic Details
Published in:Proceedings of the Royal Society. B, Biological sciences Biological sciences, 2004-05, Vol.271 (1542), p.931-939
Main Authors: Chan, Cliburn, Stark, Jaroslav, George, Andrew J. T.
Format: Article
Language:English
Subjects:
Agonists
Animals
Cellular Activation
Feedback control
Feedback, Physiological - immunology
Kinetics
Ligands
Models, Immunological
Molecules
Phosphatases
Phosphoric Monoester Hydrolases - metabolism
Phosphotransferases - metabolism
Proofreading
Receptors
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
Sensitivity and Specificity
Signal Transduction
Signal Transduction - immunology
Stochastic Processes
T cell antigen receptors
T lymphocytes
T-Cell Receptors
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Summary: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.
ISSN:0962-8452
1471-2954
DOI:10.1098/rspb.2003.2587