Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome

J Immunol. 2009 Jun 15;182(12):7672-80. doi: 10.4049/jimmunol.0800691.

Abstract

The buildup of TCR signaling microclusters containing adaptor proteins and kinases is prerequisite for T cell activation. One hallmark in this process is association of the TCR with lipid raft microdomains enriched in GPI-proteins that have potential to act as accessory molecules for TCR signaling. In this study, we show that GPI-anchored CD48 but not CD59 was recruited to the immobilized TCR/CD3 complex upon activation of T cells. CD48 reorganization was vital for T cell IL-2 production by mediating lateral association of the early signaling component linker for activated T cells (LAT) to the TCR/CD3 complex. Furthermore, we identified CD2 as an adaptor linking the Src protein tyrosine kinase Lck and the CD48/LAT complex to TCR/CD3: CD2 associated with TCR/CD3 upon T cell activation irrespective of CD48 expression, while association of CD48 and LAT with the TCR/CD3 complex depended on CD2. Consequently, our data indicate that CD2 and CD48 cooperate hierarchically in the buildup of the early TCR signalosome; CD2 functions as the master switch recruiting CD48 and Lck. CD48 in turn shuttles the transmembrane adapter molecule LAT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • CD2 Antigens / genetics
  • CD2 Antigens / immunology*
  • CD2 Antigens / metabolism
  • CD3 Complex / immunology
  • CD48 Antigen
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / immunology
  • Protein Binding
  • RNA Interference
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology
  • Time Factors

Substances

  • Antigens, CD
  • CD2 Antigens
  • CD3 Complex
  • CD48 Antigen
  • CD48 protein, human
  • Receptors, Antigen, T-Cell