Integration of the movement of signaling microclusters with cellular motility in immunological synapses

Immune synapses form between T cells and antigen-presenting cells (APCs). Increasing evidence suggests synapses must form flexibly to accommodate ongoing motility and displacement of the synapse. Here, time-lapse total internal reflection fluorescence (TIRF) microscopy showed that signaling via the T cell antigen receptor (TCR) occurred during synapse translation. TCR microclusters in motile synapses did not flow directly into supramolecular activating complexes (SMACs) but were directed, independently of myosin II contractility, toward an F-actin-poor 'sink' region. Inward microcluster flow often followed collapse of the leading edge, which suggested that actin depolymerization regulated microcluster flow and the formation of SMACs. The coordination of TCR movement with the translocation of this 'sink' shows how T cells coordinate TCR signaling and microcluster flow in dynamic physiological synapses.