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.
Wang
Hongyan
H
Department of Haematology, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Moon
Eun-Yi
EY
Azouz
Abdallah
A
Wu
Xiang
X
Smith
Andrew
A
Schneider
Helga
H
Hogg
Nancy
N
Rudd
Christopher E
CE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D005353:Fibronectins / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012190:Retroviridae; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
D005353:Fibronectins; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D010750:Phosphoproteins; C108336:SKAP1 protein, human; D018799:Intercellular Adhesion Molecule-1