Interplay between bistability and stochasticity in T-cell signaling

The stochastic dynamics of T-cell receptor (TCR) signaling are studied using a mathematical model intended to capture kinetic proofreading (sensitivity to ligand-receptor binding kinetics) and negative and positive feedback regulation. The model incorporates protein-protein interactions and reproduces several experimental observations about the behavior of TCR signaling. Analysis of the model indicates that TCR signaling dynamics are marked by significant stochastic fluctuations and bistability which is caused by the competition between the positive and negative feedbacks. Stochastic fluctuations are such that single-cell trajectories differ qualitatively from the trajectory predicted by the deterministic approximation of the dynamics. Moreover, because of the bistability, the average of single-cell trajectories differs markedly from the deterministic trajectory. Bistability combined with stochastic fluctuations allows for switch-like responses to signals, which may help a T cell to make committed cell-fate decisions.