Abstract
Src kinase–associated phosphoprotein of 55 kDa (SKAP-55; encoded by SCAP1) is a T cell adaptor protein of unknown function that contains a pleckstrin homology and an SH3 domain. Here we show that SKAP-55 regulates integrin-mediated adhesion and conjugate formation between T cells and antigen-presenting cells (APCs). SKAP-55 enhances adhesion to fibronectin and intercellular adhesion molecule-1 (ICAM-1), colocalizes with actin at the T cell–APC synapse and promotes the clustering of lymphocyte-associated antigen-1 (LFA-1). Enhanced conjugation is comparable to that induced by adhesion and degranulation–promoting adaptor protein (ADAP), a binding partner of SKAP-55, and is abrogated by deletion of the SKAP-55 SH3 domain. Conjugate formation is accompanied by the translocation of SKAP-55 to membrane rafts, an event that is regulated by both LFA-1 and T cell receptor ligation. Our findings identify a mechanism by which SKAP-55 modulates T cell responses to antigen.
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Acknowledgements
C.E.R. is the recipient of a Principal Research Fellow award from the Wellcome Trust, UK.
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Wang, H., Moon, EY., Azouz, A. et al. SKAP-55 regulates integrin adhesion and formation of T cell–APC conjugates. Nat Immunol 4, 366–374 (2003). https://doi.org/10.1038/ni913
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DOI: https://doi.org/10.1038/ni913
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