T cell receptor signalling networks: branched, diversified and bounded

Engagement of antigen-specific T cell receptors (TCRs) is a prerequisite for T cell activation. Acquisition of appropriate effector T cell function requires the participation of multiple signals from the T cell microenvironment. Trying to understand how these signals integrate to achieve specific functional outcomes while maintaining tolerance to self is a major challenge in lymphocyte biology. Several recent publications have provided important insights into how dysregulation of T cell signalling and the development of autoreactivity can result if the branching and integration of signalling pathways are perturbed. We discuss how these findings highlight the importance of spatial segregation of individual signalling components as a way of regulating T cell responsiveness and immune tolerance.