Co-stimulation and counter-stimulation: lipid raft clustering controls TCR signaling and functional outcomes

Semin Immunol. 2001 Apr;13(2):115-28. doi: 10.1006/smim.2000.0303.


T cell receptor (TCR) antigen recognition induces the formation of a specialized 'immunological synapse' at the T cell : antigen presenting cell (APC) junction. This junction is generated by the recruitment and exclusion of particular proteins from the contact area and is required for T cell activation. We and others have hypothesized that lipid raft/non-raft partitioning provides a molecular basis for protein sorting which organizes the TCR, co-stimulators, signal transducers and the actin cytoskeleton at the T cell : APC interface. Here we discuss the emerging paradigm that co-stimulators induce the directional transport and clustering of lipid rafts at the T cell : APC interface, thus generating platform(s) specialized for processive and sustained TCR signal transduction and T cell activation. We also discuss recent data implicating the involvement of 'counter-stimulators' and other negative regulators which prevent optimal raft clustering at the TCR contact site and, thus, facilitate T cell inactivation and tolerance induction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Cell Compartmentation
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytoskeleton / physiology
  • Humans
  • Lymphocyte Activation / immunology
  • Membrane Microdomains / immunology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Self Tolerance / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • Tyrosine / metabolism


  • Receptors, Antigen, T-Cell
  • Tyrosine
  • Protein-Tyrosine Kinases