Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.
Immunity. 2011 Aug 26;35(2):208-22. doi: 10.1016/j.immuni.2011.06.003. Epub 2011 Aug 4.
The immunological synapse (IS) serves a dual role for sustained T cell receptor (TCR) signaling and for TCR downregulation. TC21 (Rras2) is a RRas subfamily GTPase that constitutively associates with the TCR and is implicated in tonic TCR signaling by activating phosphatidylinositol 3-kinase. In this study, we demonstrate that TC21 both cotranslocates with the TCR to the IS and is necessary for TCR internalization from the IS through a mechanism dependent on RhoG, a small GTPase previously associated with phagocytosis. Indeed, we found that the TCR triggers T cells to phagocytose 1-6 μm beads through a TC21- and RhoG-dependent pathway. We further show that TC21 and RhoG are necessary for the TCR-promoted uptake of major histocompatibility complex (MHC) from antigen-presenting cells. Therefore, TC21 and RhoG dependence underlie the existence of a common phagocytic mechanism that drives TCR internalization from the IS together with its peptide-MHC ligand.
免疫突触 (IS) 对持续的 T 细胞受体 (TCR) 信号传导和 TCR 下调都有双重作用。TC21（Rras2）是 RRas 亚家族 GTPase，它与 TCR 持续相关，并通过激活磷脂酰肌醇 3-激酶参与 T 细胞的持续信号转导。在这项研究中，我们证明 TC21 与 TCR 一起共转位到 IS，并通过一种依赖于 RhoG 的机制对于 TCR 从 IS 内化是必需的，RhoG 是一种先前与吞噬作用相关的小 GTPase。事实上，我们发现 TCR 通过 TC21 和 RhoG 依赖途径触发 T 细胞吞噬 1-6μm 珠子。我们进一步表明，TC21 和 RhoG 对于 TCR 促进从抗原呈递细胞摄取主要组织相容性复合物 (MHC) 是必需的。因此，TC21 和 RhoG 的依赖性为 TCR 从 IS 内化与其肽-MHC 配体一起提供了一个共同的吞噬机制的存在提供了基础。
