CD81 interacts with the T cell receptor to suppress signaling.

CD81 interacts with the T cell receptor to suppress signaling.
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DOI:
10.1371/journal.pone.0050396
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Erman B
Erman B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cevik SI;Keskin N;Belkaya S;Ozlu MI;Deniz E;Tazebay UH;Erman B

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CD 81(TAPA-1)是一种广泛表达的四跨膜蛋白,被鉴定为B淋巴细胞受体(BCR)的组分和丙型肝炎病毒的受体。为了鉴定与T细胞抗原受体(TCR)相互作用的跨膜蛋白,我们进行了膜酵母双杂交筛选,并鉴定了CD 81作为TCR的CD 3 δ亚基的相互作用物。我们发现,在缺乏CD 81的情况下,在来自敲除小鼠的胸腺细胞中,TCR接合导致更强的信号。这些结果在通过shRNA介导的沉默表达低水平CD 81的T细胞系中得到了重现。增加的信号并没有导致在T淋巴细胞表面的TCR水平的改变。虽然CD 81对于正常T淋巴细胞发育不是必需的,但它通过控制信号强度在调节TCR和可能的前TCR信号转导中起重要作用。胸腺细胞信号传导中的CD 81依赖性改变在CD 81缺陷型双阳性(DP)胸腺细胞上的CD 5表达增加中是明显的。我们得出结论,CD 81与T细胞受体相互作用,抑制信号传导。
CD81 (TAPA-1) is a ubiquitously expressed tetraspanin protein identified as a component of the B lymphocyte receptor (BCR) and as a receptor for the Hepatitis C Virus. In an effort to identify trans-membrane proteins that interact with the T-cell antigen receptor (TCR), we performed a membrane yeast two hybrid screen and identified CD81 as an interactor of the CD3delta subunit of the TCR. We found that in the absence of CD81, in thymocytes from knockout mice, TCR engagement resulted in stronger signals. These results were recapitulated in T cell lines that express low levels of CD81 through shRNA mediated silencing. Increased signaling did not result from alterations in the levels of TCR on the surface of T lymphocytes. Although CD81 is not essential for normal T lymphocyte development, it plays an important role in regulating TCR and possibly pre-TCR signal transduction by controlling the strength of signaling. CD81 dependent alterations in thymocyte signaling are evident in increased CD5 expression on CD81 deficient double positive (DP) thymocytes. We conclude that CD81 interacts with the T cell receptor to suppress signaling.
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