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


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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C.E.R. is the recipient of a Principal Research Fellow award from the Wellcome Trust, UK.

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Correspondence to Christopher E. Rudd.

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