Continuous T cell receptor signaling required for synapse maintenance and full effector potential
Continuous T cell receptor signaling required for synapse maintenance and full effector potential
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DOI：
10.1038/ni951
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发表时间：
2003-08-01
影响因子：
30.5
通讯作者：
Davis, MM
中科院分区：
文献类型：
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作者：
Huppa, JB;Gleimer, M;Davis, MM
尽管通过 T 细胞受体 (TCR) 的信号对于 T 辅助细胞激活的启动至关重要，但尚不清楚这些信号在长时间的 T 细胞-抗原呈递细胞接触过程中具有什么功能。在这里，我们使用三维视频显微镜同时追踪单个 T 细胞中的 TCR-CD3 复合物和磷酸肌醇 3-激酶活性。尽管大部分 TCR-CD3 快速内化，但 TCR 依赖性信号传导在缀合物形成后 10 小时内仍然很明显。阻断这种相互作用会导致突触溶解以及白细胞介素 2 产生和细胞增殖成比例减少。因此，TCR 信号传导可持续数小时，具有累积效应，对于维持免疫突触是必需的。
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-dependant 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.