An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R

J Exp Med. 2005 Jun 6;201(11):1733-9. doi: 10.1084/jem.20042577.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / immunology
  • Cell Adhesion Molecules / immunology
  • Cell Communication / genetics
  • Cell Communication / immunology*
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Down-Regulation / immunology
  • Humans
  • Hybridomas
  • Immunologic Capping*
  • Intercellular Adhesion Molecule-1 / immunology
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Function-Associated Antigen-1 / genetics
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Mice
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • RNA, Small Interfering
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • ICAM-2 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Function-Associated Antigen-1
  • Phosphoproteins
  • RNA, Small Interfering
  • Receptors, Antigen, T-Cell
  • SKAP1 protein, human
  • src kinase associated phosphoprotein 2
  • Intercellular Adhesion Molecule-1