T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis.

T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis.
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TC21和RHOG GTPase依赖性吞噬作用介导了免疫突触的T细胞受体内在化。

DOI:
10.1016/j.immuni.2011.06.003
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发表时间:
2011-08-26
期刊:
影响因子:
32.4
通讯作者:
Alarcón B
Alarcón B
中科院分区:
医学1区
文献类型:
--
作者:
Martínez-Martín N;Fernández-Arenas E;Cemerski S;Delgado P;Turner M;Heuser J;Irvine DJ;Huang B;Bustelo XR;Shaw A;Alarcón B

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免疫突触(IS)在持续T细胞受体(TCR)信号传导和TCR下调中起双重作用。TC21 (Rras2)是RRas亚家族GTPase,与TCR组成性相关,并通过激活磷脂酰肌醇3-激酶参与强直性TCR信号传导。在这项研究中,我们证明TC21既与TCR共同易位到IS,又通过依赖于RhoG的机制使TCR从IS内化。RhoG是一种小的GTPase,以前被认为与吞噬有关。事实上,我们发现TCR通过TC21和rhog依赖途径触发T细胞吞噬1-6 μm微球。我们进一步证明TC21和RhoG对于tcr促进抗原提呈细胞摄取主要组织相容性复合体(MHC)是必需的。因此,TC21-和rhog依赖性是一种共同的吞噬机制的基础,该机制驱动IS及其肽- mhc配体的TCR内化。
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 co-translocates 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 been 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.
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