Editors' ChoiceImmunology

Motoring Along the Immunological Synapse

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Science Signaling  28 Apr 2009:
Vol. 2, Issue 68, pp. ec149
DOI: 10.1126/scisignal.268ec149

The formation of the immunological synapse (IS) between a T cell and an antigen-presenting cell (APC) is a well-studied process; however, various mechanistic aspects of IS formation are unclear. When the T cell receptor (TCR) is engaged by peptide-loaded major histocompatability complex on the APC, TCR microclusters form at the periphery of the IS and then move by centripetal actin flow to the center, the central supramolecular activation cluster (cSMAC). Ilani et al. now provide evidence that the actin-based motor protein nonmuscle myosin IIA is critical for stabilization of the IS and the generation of signals downstream of the TCR. Through imaging studies of Jurkat T cells that interacted with planar lipid bilayers or with APCs, the authors showed that inhibition of the activity of myosin IIA through blebbistatin or siRNA-mediated knockdown of myosin IIA impeded the movement of TCR microclusters to the cSMAC. Western blotting showed that stimulation of the TCR triggered the prolonged phosphorylation of myosin light chain, a hallmark of the activation of myosin IIA. The half-life of preformed IS was shorter in blebbistatin-treated cells than in control cells, but this was not due to any defect in the function of adhesion molecules. TCR-triggered Ca2+ responses were lower and less sustained in blebbistatin-treated cells than in untreated cells. This correlated with a defect in the phosphorylation of the TCR-associated proteins ZAP70 and LAT, but not the more upstream kinase Lck, in myosin IIA–deficient cells compared with that in control cells. Together, these data suggest a role for myosin IIA in mediating IS stabilization and downstream TCR signaling.

T. Ilani, G. Vasiliver-Shamis, S. Vardhana, A. Bretscher, M. L. Dustin, T cell antigen receptor signaling and immunological synapse stability require myosin IIA. Nat. Immunol. 10, 531–539 (2009). [PubMed]

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