Immunological synapse formation licenses CD40-CD40L accumulations at T-APC contact sites

J Immunol. 2004 Sep 15;173(6):3647-52. doi: 10.4049/jimmunol.173.6.3647.

Abstract

The maintenance of tolerance is likely to rely on the ability of a T cell to polarize surface molecules providing "help" to only specific APCs. The formation of a mature immunological synapse leads to concentration of the TCR at the APC interface. In this study, we show that the CD40-CD154 receptor-ligand pair is also highly concentrated into a central region of the synapse on mouse lymphocytes only after the formation of the TCR/CD3 c-SMAC. Concentration of this ligand was strictly dependent on TCR recognition, the binding of ICAM-1 to T cell integrins and the presence of an intact cytoskeleton in the T cells. This may provide a novel explanation for the specificity of T cell help directing the help signal to the site of Ag receptor signal. It may also serve as a site for these molecular aggregates to coassociate and/or internalize alongside other signaling receptors.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Bacterial Proteins / genetics
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism*
  • CD40 Antigens / physiology
  • CD40 Ligand / biosynthesis
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism*
  • Cell Communication / immunology*
  • Clone Cells
  • Cytoskeleton / immunology
  • Cytoskeleton / metabolism
  • Epitopes, T-Lymphocyte / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Intercellular Adhesion Molecule-1 / physiology
  • Luminescent Proteins / genetics
  • Lymphocyte Activation* / genetics
  • Mice
  • Mice, Inbred AKR
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Plasmids
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Bacterial Proteins
  • CD40 Antigens
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Luminescent Proteins
  • Peptide Fragments
  • Receptor-CD3 Complex, Antigen, T-Cell
  • yellow fluorescent protein, Bacteria
  • Intercellular Adhesion Molecule-1
  • CD40 Ligand