Publications [#278112] of Chi Wei C. Chan

Papers Published

1. Chan, C; Stark, J; George, AJT, Feedback control of T-cell receptor activation., Proc Biol Sci, vol. 271 no. 1542 (May, 2004), pp. 931-939, ISSN 0962-8452 [15255048], [doi]
   (last updated on 2026/01/16)

   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.

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