Continuous T cell receptor signaling required for synapse maintenance and full effector potential

Nat Immunol. 2003 Aug;4(8):749-55. doi: 10.1038/ni951. Epub 2003 Jul 13.


Although signals through the T cell receptor (TCR) are essential for the initiation of T helper cell activation, it is unclear what function such signals have during the prolonged T cell-antigen-presenting cell contact. Here we simultaneously tracked TCR-CD3 complex and phosphoinositide 3-kinase activity in single T cells using three-dimensional video microscopy. Despite rapid internalization of most of the TCR-CD3, TCR-dependent signaling was still evident up to 10 h after conjugate formation. Blocking this interaction caused dissolution of the synapse and proportional reductions in interleukin 2 production and cellular proliferation. Thus TCR signaling persists for hours, has a cumulative effect and is necessary for the maintenance of the immunological synapse.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Calcium / immunology
  • Calcium / metabolism
  • Cell Communication / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • CD3 Complex
  • CD3 antigen, zeta chain
  • Receptors, Antigen, T-Cell
  • Calcium