A Logical Analysis of Timing-Dependent Signaling Properties in the Immune System
Wednesday, October 14, 1998 - 2:30pm - 3:00pm
Marcelline Kaufman (Université Libre de Bruxelles)
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 termed 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 engagement, the mechanism by which a same receptor can induce alternative cellular responses is not completely understood. Here, we present a model for explaining both positive (cytokine production and cell proliferation) and negative (anergy induction) signaling of T lymphocytes. This model relies on the autophosphorylative properties of the tyrosine kinases associated with the T-cell receptor and consists of a chain of interconnected events each of which requiring a characteristic time to be realized. Using a simple Boolean formalism, we show how the timing of the successive events can affect the properties of receptor signaling and determine the type of cellular response. Our approach integrates into a common framework a large body of experimental observations and allows to specify conditions leading to cellular activation or to energy.