TCR Microclusters pre-exist and contain molecules necessary for TCR signal transduction

J Immunol. 2014 Jul 1;193(1):56-67. doi: 10.4049/jimmunol.1400315. Epub 2014 May 23.

Abstract

TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These pre-existing microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters linker for activation of T cells and growth factor receptor-bound protein 2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could explain, in part, the rapid kinetics with which TCR signal transduction occurs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / immunology*
  • Membrane Microdomains / genetics
  • Membrane Microdomains / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens
  • Ptprc protein, mouse