Nature Reviews Immunology 13, 257-269 (April 2013) | doi:10.1038/nri3403

T cell receptor signalling networks: branched, diversified and bounded

Rebecca J. Brownlie1 & Rose Zamoyska1  About the authors


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.

Author affiliations

  1. Institute for Immunology and Infection Research, The University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.

Correspondence to: Rose Zamoyska1 Email:

Published online 25 March 2013