On Rare Events in T Cell Activation

Abstract

T cell activation is a stochastic process occurring over a finite time interaction with an anti-gen presenting cell (APC). The T cell commits to activation based on a finite number of T cell receptor phosphorylation events; the high specificity and sensitivity of T cells indicating that information on ligand quality can be extracted with precision. We examine a mathemat-ical model for T cell activation based on a number of criteria, or strategies, that utilise the history of TCR phosphorylation to discriminate ligands. We justify our model using exper-imental data in a situation where one of the key co-receptors on the T cell surface, namely the CD4 receptor is blocked. A dual threshold-strategy with a temporal treatment turns out to perform better in discriminating agonist peptides than a single-threshold strategy for T cell’s activation. We employ the Wentzell-Friedlin theory for large deviations in stochastic processes [5,13] to determine the activation probabilitites.