A logical analysis of T cell activation and anergy

Interaction of the antigen-specific receptor of T lymphocytes with its anti genic ligand can lead either to cell activation or to a state of profound u nresponsiveness (anergy), Although subtle changes in the nature of the liga nd 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 i nduce alternative cellular responses is not completely understood. A model for explaining both positive (cell proliferation and cytokine production) a nd negative (anergy induction) signaling of T lymphocytes is described here in. 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 ab ove background level after ligand removal and is responsible for cellular u nresponsiveness. Using a simple Boolean formalism, we show how the timing o f the binding and intracellular signal-transduction events can affect the p roperties of receptor signaling and determine the type of cellular response . The present approach integrates into a common framework a large body of e xperimental observations and allows specification of conditions leading to cellular activation or to anergy.