Research ArticleTCR Signaling

Dynamics of Subsynaptic Vesicles and Surface Microclusters at the Immunological Synapse

Sci. Signal.  11 May 2010:
Vol. 3, Issue 121, pp. ra36
DOI: 10.1126/scisignal.2000645

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Submariner Adaptor

Engagement of the T cell antigen receptor (TCR) on the surface of a T cell with peptide-loaded major histocompatibility complex on the surface of an antigen-presenting cell occurs at a specialized contact point known as the immunological synapse (IS). Stimulation of the TCR triggers the activation of the proximal kinases Lck and ZAP-70, which leads to the formation at the IS of microclusters of kinases and adaptor molecules that are required for T cell signaling. Two of these adaptor molecules are the cytosolic protein SLP-76 and the plasma membrane–associated protein LAT. SLP-76 and LAT form distinct microclusters, but how they interact to propagate T cell signals is unclear (see the Perspective by Billadeau). Purbhoo et al. used imaging techniques to show that a fraction of LAT was enriched in intracellular vesicles that resided below the IS and that these vesicles moved to the IS, where they interacted with SLP76-containing microclusters. LAT-containing vesicles were corralled by TCR–ZAP-70 microclusters in the IS and were more mobile than the SLP-76 microclusters, but they slowed when they interacted with SLP-76. Cells that contained a mutant LAT that could not interact with SLP-76 (through the associated protein GADS) contained fewer SLP-76 microclusters, and LAT-containing vesicles interacted less with them. Together, these data suggest that vesicular LAT interacts with protein microclusters at the IS and contributes to the propagation of T cell signaling.

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