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Mechanism and function of Vav1 localisation in TCR signalling
Olga Ksionda, Alexander Saveliev, Robert Köchl, Jonathan Rapley, Mustapha Faroudi, Jennifer E. Smith-Garvin, Christoph Wülfing, Katrin Rittinger, Tom Carter, Victor L. J. Tybulewicz


The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4+ and CD8+ T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3B) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3B domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.


  • *Present address: University of California, San Francisco, CA 94143, USA

  • Present address: Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK

  • §Present address: Fujifilm Diosynth Biotechnologies UK Ltd, Belasis Avenue, Billingham TS23 1LH, UK

  • Present address: Centre d'Immunologie Marseille Luminy, Marseille, France

  • **Present address: Fox Chase Cancer Center, Philadelphia, PA 19111, USA

  • ‡‡Present address: University of Bristol, Bristol, BS8 1TD, UK

  • Funding

    M.F. was a recipient of an EMBO long-term fellowship (fellowship number ALTF 508-2005) and a EU Marie Curie fellowship. (fellowship number EIF 025449). O.K., A.S., J.R., K.R., T.C. and V.T. were funded by the UK Medical Research Council programme [grant numbers U117527252, U117565398 and U117573808]; R.K. was supported by Wellcome Trust [grant number 089185]. Deposited in PMC for immediate release.

  • Supplementary material available online at

  • Accepted August 8, 2012.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (, which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.

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