Research ArticleImmunology

Itk Controls the Spatiotemporal Organization of T Cell Activation

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Science Signaling  04 Oct 2011:
Vol. 4, Issue 193, pp. ra66
DOI: 10.1126/scisignal.2001821

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Focused on the Center

After T cell receptor (TCR) stimulation by an antigen-presenting cell (APC), an array of proteins are recruited to the T cell side of the interface with the APC (the immunological synapse), where they generate signals that activate the T cell. Singleton et al. provide data showing that interleukin-2 (IL-2)–inducible T cell kinase (Itk) plays a central role in directing “molecular traffic” at the immunological synapse. By comparing the organization of fluorescent sensors of T cell signaling molecules between antigen-activated wild-type and Itk-deficient T cells, the authors found that loss of Itk resulted in the inappropriate spatial organization of many signaling proteins at the T cell–APC interface, which impaired T cell activation. In particular, Itk was required to direct the activation of the guanosine triphosphatase Cdc42 at the center of the synapse, which led to appropriate actin accumulation downstream of TCR activation. Together, these data establish a central role for Itk in the organization of T cell signaling molecules and provide evidence for the dependence of critical T cell functions on the spatiotemporal organization of signaling intermediates.