National French Institute of Health and Medical Research (INSERM) 1149, Center of Research on Inflammation, Paris, France.
National French Center of Scientific Research (CNRS) ERL8252, Paris, France.
Immunol Rev. 2019 Sep;291(1):57-74. doi: 10.1111/imr.12764.
T-lymphocyte activation relies on the cognate recognition by the TCR of the MHC-associated peptide ligand (pMHC) presented at the surface of an antigen-presenting cell (APC). This leads to the dynamic formation of a cognate contact between the T lymphocyte and the APC: the immune synapse (IS). Engagement of the TCR by the pMHC in the synaptic zone induces a cascade of signaling events leading to phosphorylation and dephosphorylation of proteins and lipids, which ultimately shapes the response of T lymphocytes. Although the engagement of the T-cell receptor (TCR) takes place at the plasma membrane, the TCR/CD3 complexes and the signaling molecules involved in transduction of the TCR signal are also present in intracellular membrane pools. These pools, which are both endocytic and exocytic, have tentatively been characterized by several groups including ours. We will herein summarize what is known on the intracellular pools of TCR signaling components. We will discuss their origin and the mechanisms involved in their mobility at the IS. Finally, we will propose several hypotheses concerning the functional role(s) that these intracellular pools might play in T-cell activation. We will also discuss the tools that could be used to test these hypotheses.
T 淋巴细胞的激活依赖于 T 细胞受体(TCR)对存在于抗原呈递细胞(APC)表面的 MHC 相关肽配体(pMHC)的同源识别。这导致 T 淋巴细胞和 APC 之间形成一个同源接触:免疫突触(IS)。pMHC 在突触区与 TCR 的结合诱导一系列信号事件,导致蛋白质和脂质的磷酸化和去磷酸化,最终塑造 T 淋巴细胞的反应。尽管 T 细胞受体(TCR)的结合发生在质膜上,但 TCR/CD3 复合物和参与 TCR 信号转导的信号分子也存在于细胞内膜池中。这些池既是内吞的又是外排的,已经被包括我们在内的几个小组进行了特征描述。我们将在此总结关于 TCR 信号传导成分的细胞内池的已知内容。我们将讨论它们的起源以及它们在 IS 处的流动性所涉及的机制。最后,我们将提出几个假设,这些假设涉及这些细胞内池在 T 细胞激活中可能发挥的功能作用。我们还将讨论可以用来检验这些假设的工具。