Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation.

Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation.
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HAb18G/CD147 参与 T 细胞激活和免疫突触形成

DOI:
10.1111/j.1582-4934.2010.01012.x
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发表时间:
2010-08
影响因子:
5.3
通讯作者:
Chen Z
Chen Z
中科院分区:
医学2区
文献类型:
--
作者:
Hu J;Dang N;Yao H;Li Y;Zhang H;Yang X;Xu J;Bian H;Xing J;Zhu P;Chen Z

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HAb 18 G/CD 147是免疫球蛋白超家族(IgSF)的糖蛋白,是T细胞活化相关分子。在本报告中,我们证明了活化的CD 4+和CD 8 + T细胞上的HAb 18 G/CD 147表达上调。在体外交联的T细胞与抗HAb 18 G/CD 147单克隆抗体(mAb)5A 12抑制T细胞增殖后,T细胞受体刺激。这种共刺激通过下调CD 25和白细胞介素2(IL-2)的表达来抑制T细胞增殖,减少IL-4的产生,但不影响干扰素-γ的产生。激光共聚焦成像分析表明,在T细胞活化过程中,HAb 18 G/CD 147被募集到免疫突触(IS);通过抗HAb 18 G/CD 147 mAb 5A 12触发活化的T细胞上的HAb 18 G/CD 147强烈分散IS的形成。进一步的功能研究表明,HAb 18 G/CD 147与mAb 5A 12的连接降低了T细胞的酪氨酸磷酸化和细胞内钙动员水平。通过对接抗体-抗原相互作用,我们证明了mAb 5A 12的功能紧密依赖于其与N端结构域I的特异性结合,该结构域I在HAb 18 G/CD 147的寡聚化中起关键作用。综上所述,我们提供的证据表明,HAb 18 G/CD 147可以作为一个共刺激受体,负调节T细胞活化,并在功能上与IS的形成。
HAb18G/CD147, a glycoprotein of the immunoglobulin super-family (IgSF), is a T cell activation-associated molecule. In this report, we demonstrated that HAb18G/CD147 expression on both activated CD4+ and CD8+ T cells was up-regulated. In vitro cross-linking of T cells with an anti-HAb18G/CD147 monoclonal antibody (mAb) 5A12 inhibited T cells proliferation upon T cell receptor stimulation. Such co-stimulation inhibited T cell proliferation by down-regulating the expression of CD25 and interleukin-2 (IL-2), decreased production of IL-4 but not interferon-γ. Laser confocal imaging analysis indicated that HAb18G/CD147 was recruited to the immunological synapse (IS) during T cell activation; triggering HAb18G/CD147 on activated T cells by anti-HAb18G/CD147 mAb 5A12 strongly dispersed the formation of the IS. Further functional studies showed that the ligation of HAb18G/CD147 with mAb 5A12 decreased the tyrosine phosphorylation and intracellular calcium mobilization levels of T cells. Through docking antibody–antigen interactions, we demonstrated that the function of mAb 5A12 is tightly dependent on its specificity of binding to N-terminal domain I, which plays pivotal role in the oligomerization of HAb18G/CD147. Taken together, we provide evidence that HAb18G/CD147 could act as a co-stimulatory receptor to negatively regulate T cell activation and is functionally linked to the formation of the IS.
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