A logical analysis of T cell activation and anergy.
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.
Kaufman
M
M
Université Libre de Bruxelles, Centre for Nonlinear Phenomena and Complex Systems, Campus Plaine CP 231, 1050 Brussels, Belgium. mkaufma@ulb.ac.be
Andris
F
F
Leo
O
O
D000818:Animals; D017635:Clonal Anergy; D008128:Logic; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D018448:Models, Immunological; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases