A logical analysis of T cell activation and anergy
Open Access
- 30 March 1999
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 96 (7), 3894-3899
- https://doi.org/10.1073/pnas.96.7.3894
Abstract
Interaction of the antigen-specific receptor of T lymphocytes with its antigenic ligand can lead either to cell activation or to a state of profound unresponsiveness (anergy). Although subtle changes in the nature of the ligand or of the antigen-presenting cell have been shown to affect the outcome of T cell receptor ligation, the mechanism by which the same receptor can induce alternative cellular responses is not completely understood. A model for explaining both positive (cell proliferation and cytokine production) and negative (anergy induction) signaling of T lymphocytes is described herein. This model relies on the autophosphorylative properties of the tyrosine kinases associated with the T cell receptor. One of its basic assumptions is that the kinase activity of these receptor-associated enzymes remains above background level after ligand removal and is responsible for cellular unresponsiveness. Using a simple Boolean formalism, we show how the timing of the binding and intracellular signal-transduction events can affect the properties of receptor signaling and determine the type of cellular response. The present approach integrates into a common framework a large body of experimental observations and allows specification of conditions leading to cellular activation or to anergy.Keywords
This publication has 36 references indexed in Scilit:
- Altered T Cell Receptor Ligands Trigger a Subset of Early T Cell SignalsImmunity, 1996
- T Cell Activation Determined by T Cell Receptor Number and Tunable ThresholdsScience, 1996
- A TCR Binds to Antagonist Ligands with Lower Affinities and Faster Dissociation Rates Than to AgonistsImmunity, 1996
- Induction of T cell unresponsiveness by anti‐CD3 antibodies occurs independently of co‐stimulatory functionsEuropean Journal of Immunology, 1996
- Kinetic discrimination in T-cell activation.Proceedings of the National Academy of Sciences, 1996
- Induction of the increased Fyn kinase activity in anergic T helper type 1 clones requires calcium and protein synthesis and is sensitive to cyclosporin AEuropean Journal of Immunology, 1995
- Kinetic proofreading in T-cell receptor signal transduction.Proceedings of the National Academy of Sciences, 1995
- Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cellsNature, 1994
- Regulatory networks seen as asynchronous automata: A logical descriptionJournal of Theoretical Biology, 1991
- Towards a logical analysis of the immune responseJournal of Theoretical Biology, 1985