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

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

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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.


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.

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