A large T cell invagination with CD2 enrichment resets receptor engagement in the immunological synapse

J Immunol. 2006 Oct 1;177(7):4402-13. doi: 10.4049/jimmunol.177.7.4402.

Abstract

T cell activation is driven by the TCR and complemented by costimulation. We have studied the dynamics of ligand-engagement of the costimulatory receptor CD2 in T cell/APC couples. Thousands of ligand-engaged CD2 molecules were included in a large T cell invagination at the center of the cellular interface within 1 min of cell couple formation. The structure and regulation of this invagination shared numerous features with phagocytosis and macropinocytosis. Three observations further characterize the invagination and the inclusion of CD2: 1) numerous ligand-engaged receptors were enriched in and internalized through the T cell invagination, none as prominently as CD2; 2) dissolution of the T cell invagination and CD2 engagement were required for effective proximal T cell signaling; and 3) the T cell invagination was uniquely sensitive to the affinity of the TCR for peptide-MHC. Based on this characterization, we speculate that the T cell invagination, aided by CD2 enrichment, internalizes parts of the TCR signaling machinery to reset T cell signaling upon agonist-mediated, stable APC contact.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / ultrastructure*
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • CD2 Antigens / immunology
  • CD2 Antigens / metabolism*
  • CD48 Antigen
  • Endocytosis / immunology
  • Image Processing, Computer-Assisted
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / ultrastructure*

Substances

  • Actins
  • Antigens, CD
  • CD2 Antigens
  • CD48 Antigen
  • Receptors, Antigen, T-Cell