Continuous T cell receptor signaling required for synapse maintenance and full effector potential.
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.
Huppa
Johannes B
JB
Stanford University School of Medicine, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, Beckman Center B221, 279 Campus Drive, Stanford, California 94305, USA.
Gleimer
Michael
M
Sumen
Cenk
C
Davis
Mark M
MM
D000818:Animals; D017951:Antigen Presentation; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D011948:Receptors, Antigen, T-Cell; D002118:Calcium