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Sci. Signal., 4 October 2011
Vol. 4, Issue 193, p. ra66
[DOI: 10.1126/scisignal.2001821]

RESEARCH ARTICLES

Itk Controls the Spatiotemporal Organization of T Cell Activation

Kentner L. Singleton1, Monica Gosh1, Radhika D. Dandekar1, Byron B. Au-Yeung2, Olga Ksionda3, Victor L. J. Tybulewicz3, Amnon Altman4, Deborah J. Fowell2, and Christoph Wülfing1,5*

1 Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2 David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
3 Division of Immune Cell Biology, Medical Research Council, National Institute for Medical Research, London NW7 1AA, UK.
4 Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
5 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract: During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)–inducible T cell kinase (Itk) in mice altered the spatiotemporal distributions of 14 of 16 sensors of T cell signaling molecules in the region of the interface between the T cell and the APC, which reduced the segregation of signaling intermediates into distinct spatiotemporal patterns. Activation of the Rho family guanosine triphosphatase Cdc42 at the center of the cell-cell interface was impaired, although the total cellular amount of active Cdc42 remained intact. The defect in Cdc42 localization resulted in impaired actin accumulation at the T cell–APC interface in Itk-deficient T cells. Reconstitution of cells with active Cdc42 that was specifically directed to the center of the interface restored actin accumulation in Itk-deficient T cells. Itk also controlled the central localization of the guanine nucleotide exchange factor SLAT [Switch-associated protein 70 (SWAP-70)–like adaptor of T cells], which may contribute to the activation of Cdc42 at the center of the interface. Together, these data illustrate how control of the spatiotemporal organization of T cell signaling controls critical aspects of T cell function.

* To whom correspondence should be addressed. E-mail: christoph.wuelfing{at}UTSouthwestern.edu

Citation: K. L. Singleton, M. Gosh, R. D. Dandekar, B. B. Au-Yeung, O. Ksionda, V. L. J. Tybulewicz, A. Altman, D. J. Fowell, C. Wülfing, Itk Controls the Spatiotemporal Organization of T Cell Activation. Sci. Signal. 4, ra66 (2011).

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