Modulation of T cell activation by stomatin-like protein 2.

Modulation of T cell activation by stomatin-like protein 2.
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DOI:
10.4049/jimmunol.181.3.1927
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发表时间:
2008-08-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Madrenas J
Madrenas J
中科院分区:
其他
文献类型:
--
作者:
Kirchhof MG;Chau LA;Lemke CD;Vardhana S;Darlington PJ;Márquez ME;Taylor R;Rizkalla K;Blanca I;Dustin ML;Madrenas J

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通过抗原受体(TCR)的T细胞活化需要来自质膜中的脂筏微域内的信号体的持续信号传导。在从人类T细胞的脂筏的蛋白质组学分析中,我们确定了气孔蛋白样蛋白2(SLP-2)作为一个候选分子参与通过抗原受体的T细胞活化。在这里,我们表明,SLP-2表达在人类初级淋巴细胞上调后,在体内和体外激活。在活化的T细胞中,SLP-2与TCR信号体的组分和聚合的肌动蛋白相互作用。更重要的是,人T细胞系和原代外周血T细胞中SLP-2表达的上调增加效应子应答,而SLP- 2表达的下调与持续TCR信号传导的丧失和T细胞活化的降低相关。我们的数据表明,SLP-2是一个重要的球员在T细胞活化,通过确保持续的TCR信号,这是完全效应T细胞分化所需的,并指出SLP-2作为免疫调节的潜在目标。
T cell activation through the antigen receptor (TCR) requires sustained signalling from signalosomes within lipid rafts microdomains in the plasma membrane. In a proteomic analysis of lipid rafts from human T cells, we identified stomatin-like protein 2 (SLP-2) as a candidate molecule involved in T cell activation through the antigen receptor. Here, we show that SLP-2 expression in human primary lymphocytes is up-regulated following in vivo and ex vivo activation. In activated T cells, SLP-2 interacts with components of TCR signalosomes and with polymerized actin. More importantly, up-regulation of SLP-2 expression in human T cell lines and primary peripheral blood T cells increases effector responses while down-regulation of SLP- 2 expression correlates with loss of sustained TCR signalling and decreased T cell activation. Our data suggest that SLP-2 is an important player in T cell activation by ensuring sustained TCR signalling, which is required for full effector T cell differentiation, and point to SLP-2 as a potential target for immunomodulation.
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