Too fast to die

Signals generated by the T cell receptor (TCR) result in the death or survival of developing thymocytes (T cell precursors), depending on the affinity of the TCR for peptide ligands bound to the major histocompatibility complex (MHC) that are encountered in the thymus. A new study by Ellen Robey's group in this issue of Science Signaling presents a systematic evaluation of signaling and motility changes in thymocytes that encounter ligands of different affinities in the thymic environment. In contrast to previous in vitro studies, the authors found that low-affinity ligands stimulated infrequent transient mobilization of intracellular Ca(2+), whereas high-affinity ligands triggered sustained Ca(2+) signaling and periods of migratory arrest. For ligands of intermediate affinity, changes in thymocyte motility, rather than in Ca(2+) signaling patterns, provided the best correlation with functional outcomes. These findings suggest that transient signaling events in the absence of strong stop signals are required for thymocyte survival and functional maturation in the thymus.