Transient selection in multi-cellular immune networks

We analyze the dynamics of a multi-clonotype naive T-cell population competing for survival signals from antigen-presenting cells. We find that this competition provides with an efficacious selection of clonotypes, making the less able and more repetitive get extinct. We uncover the scaling principles for large systems the extinction rate obeys and calibrate the model parameters to their experimental counterparts. For the first time we estimate the physiological values of the T-cell receptor – antigen presentation profile recognition probability and T-cell clonotypes niche overlap. We demonstrate that, while the ultimate state is a stable fixed point, sequential transients dominate the dynamics over large timescales that may span over years, if not decades, in real time. We argue that what is currently viewed as ‘homeostasis’ is a complex sequential transient process, while being quasi-stationary in the total number of T-cells only. The discovered type of sequential transient dynamics in large random networks is a novel alternative to the stable heteroclinic channel mechanism.