The balance between T cell receptor signaling and degradation at the center of the immunological synapse is determined by antigen quality

Immunity. 2008 Sep 19;29(3):414-22. doi: 10.1016/j.immuni.2008.06.014. Epub 2008 Aug 28.


The role of the center of the immunological synapse (the central supramolecular activation cluster or cSMAC) is controversial. One model suggests that the role of the cSMAC depends on antigen quality and can both enhance signaling and receptor downregulation, whereas a second model proposes that the sole function of the cSMAC is to downregulate signaling. An important distinction between the models is whether signaling occurs in the cSMAC. Here, we demonstrate that at early time points, signaling occurs outside the cSMAC, but occurs in the cSMAC at later time points. Additionally, we show that cSMAC formation enhances the stimulatory potency of weak agonists for the TCR. Combined with previous studies showing that cSMAC formation decreases the signaling by strong agonists, our data support a model proposing that signaling and receptor degradation both occur in the cSMAC and that the balance between signaling and degradation in the synapse is determined by antigen quality.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Down-Regulation
  • HeLa Cells
  • Humans
  • Intercellular Junctions / metabolism*
  • Mice
  • Mice, Transgenic
  • Peptides / immunology*
  • Peptides / metabolism
  • Phosphatidylinositols / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • Transfection
  • ZAP-70 Protein-Tyrosine Kinase / metabolism*


  • Peptides
  • Phosphatidylinositols
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • Phosphotyrosine
  • ZAP-70 Protein-Tyrosine Kinase