Research ArticleImmunology

The tyrosine phosphatase SHP-1 promotes T cell adhesion by activating the adaptor protein CrkII in the immunological synapse

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Sci. Signal.  08 Aug 2017:
Vol. 10, Issue 491, eaal2880
DOI: 10.1126/scisignal.aal2880

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Shaping T cell activation

Efficient activation of the T cell receptor (TCR) on T cells by antigen-presenting cells (APCs) requires the formation of a stable interface (the immunological synapse) between both cell types. T cell adhesion to APCs is mediated by the T cell integrin LFA-1, the activation of which depends on the small guanosine triphosphatase (GTPase) Rap1. Patients with mutations in the gene encoding Rap1 have an immunodeficiency caused by defective T cell adhesion. Azoulay-Alfaguter et al. used live-cell imaging to show that the adaptor protein CrkII, which is required for Rap1 activation, was recruited from the central region of the immunological synapse to the peripheral region where Rap1 and LFA-1 were localized. This translocation depended on the TCR-stimulated activity of the phosphatase SHP-1, which dephosphorylated the inactive (phosphorylated) form of CrkII. Together, these data suggest that targeting the phosphorylation state of CrkII may enable therapeutic modulation of T cell adhesion and activation.