An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R.
Lymphocyte function-associated antigen (LFA)-1 clustering, which is needed for high avidity binding to intercellular adhesion molecule (ICAM)-1 and -2, regulates T cell motility and T cell-antigen-presenting cell (APC) conjugation. In this study, down-regulation of SKAP-55 by small interfering RNAs (siRNAs) identified an essential role for this adaptor molecule in the T cell receptor (TCR)-mediated "inside-out signaling" that is needed for LFA-1 clustering and T cell-APC conjugation. In contrast, down-regulation of SKAP-55 had no effect on TCR-CD3 clustering. Furthermore, the expression of the related protein SKAP-55R failed to compensate for the loss of SKAP-55 in LFA-1 clustering, indicating that SKAP-55 has a unique function that cannot be replaced by this closely related protein. Our findings therefore indicate that SKAP-55, unlike SKAP-55R, is specifically tailored as an essential component of the inside-out signaling events that couple the TCR to LFA-1 clustering and T cell-APC conjugation.
Jo
Eun-Kyeong
EK
Molecular Immunology Section, Department of Immunology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 ONN, England, UK.
Wang
Hongyan
H
Rudd
Christopher E
CE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D007152:Immunologic Capping; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; C108336:SKAP1 protein, human; C116431:src kinase associated phosphoprotein 2; D018799:Intercellular Adhesion Molecule-1