T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster

Immunity. 2006 Jul;25(1):117-27. doi: 10.1016/j.immuni.2006.04.010.


T cell receptor (TCR) signaling is initiated and sustained in microclusters; however, it's not known whether signaling also occurs in the TCR-rich central supramolecular activation cluster (cSMAC). We showed that the cSMAC formed by fusion of microclusters contained more CD45 than microclusters and is a site enriched in lysobisphosphatidic acid, a lipid involved in sorting ubiquitinated membrane proteins for degradation. Calcium signaling via TCR was blocked within 2 min by anti-MHCp treatment and 1 min by latrunculin-A treatment. TCR-MHCp interactions in the cSMAC survived these perturbations for 10 min and hence were not sufficient to sustain signaling. TCR microclusters were also resistant to disruption by anti-MHCp and latrunculin-A treatments. We propose that TCR signaling is sustained by stabilized microclusters and is terminated in the cSMAC, a structure from which TCR are sorted for degradation. Our studies reveal a role for F-actin in TCR signaling beyond microcluster formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Antibodies / immunology
  • Cells, Cultured
  • Histocompatibility Antigens / immunology
  • Leukocyte Common Antigens / immunology
  • Lipid Metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Protein Binding
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • ZAP-70 Protein-Tyrosine Kinase / metabolism


  • Actins
  • Antibodies
  • Histocompatibility Antigens
  • Receptors, Antigen, T-Cell
  • ZAP-70 Protein-Tyrosine Kinase
  • Leukocyte Common Antigens