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SKAP-55 regulates integrin adhesion and formation of T cell–APC conjugates

Nature Immunology volume 4, pages 366–374 (2003)Cite this article

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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Figure 1: Expression of SKAP-55 enhances T cell adhesion to APCs.
Figure 2: SKAP-55 and ADAP enhance conjugate formation.
Figure 3: SKAP-55 enhances integrin binding to fibronectin and ICAM-1.
Figure 4: SKAP-55 potentiates integrin binding and conjugate formation in retroviral transduction of primary T cells.
Figure 5: SKAP-55 localizes at the contact region between T cells and anti-CD3 beads or APCs.
Figure 6: SKAP-55 translocates to membrane lipid rafts during conjugate formation.
Figure 7: LFA-1 and TCR-CD3 ligation induces SKAP-55 translocation to lipid rafts.
Figure 8: SKAP-55 promotes integrin clustering and capping on the surface of T cells.

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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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  1. Hongyan Wang and Eun-Yi Moon: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Haematology, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Hongyan Wang, Xiang Wu, Helga Schneider & Christopher E. Rudd

  2. Division of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Eun-Yi Moon, Abdallah Azouz, Helga Schneider & Christopher E. Rudd

  3. Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Eun-Yi Moon & Christopher E. Rudd

  4. Department of Medicine, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Abdallah Azouz, Helga Schneider & Christopher E. Rudd

  5. Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London, W2A 3PX, UK

    Andrew Smith & Nancy Hogg

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Correspondence to Christopher E. Rudd.

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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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