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首页> 外文期刊>International Journal of Biological Macromolecules: Structure, Function and Interactions >Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies
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Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies

机译:LCRV蛋白从yersinia pestis与人t细胞的结合诱导细胞凋亡,其完全被特异性抗体阻断

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The V antigen (LcrV) of the plague bacterium Yersinia pestis is a potent protective protein that is considered as a vaccine component for humans. LcrV mediates the delivery of Yop toxins into host cells and upregulates TLR2-dependent IL-10 production. Although LcrV can interact with the receptor-bound human interferon-gamma (hIFN-gamma), the significance of these interactions in plague pathogenesis is not known. In this study, we determined the parameters of specific interactions of LcrV and LcrV(68-326) with primary human thymocytes and Jurkat T-leukemia cells in the presence of receptor-bound hIFN-gamma. Although the C-terminal region of hIFN-gamma contains a GRRA(138-141) site needed for high-affinity binding of LcrV and LcrV(68-326), in the hIFN-gamma homodimer, these GRRA(138-141) target sites becomes accessible for targeting by LcrV or LcrV(68-326) only after immobilization of the hIFN-gamma homodimer on the hIFN-gamma receptors of thymocytes or Jurkat T-cells. The interaction of LcrV or LcrV(68-326) with receptor-bound hIFN-gamma on the thymocytes or Jurkat T-cells caused apoptosis of both cell types, which can be completely blocked by the addition of monoclonal antibodies specific to the LEEL32-35 and DEEI203-206 sites of LcrV. The ability of LcrV to utilize hIFN-gamma is insidious and may account in part for the severe symptoms of plague in humans. (C) 2018 Elsevier B.V. All rights reserved.
机译:瘟疫菌菌瘟疫的v抗原(LCRV)是一种有效的保护性蛋白,被认为是人类的疫苗组分。 LCRV介导YOP毒素的递送到宿主细胞中,并推动TLR2依赖性IL-10生产。尽管LCRV可以与受体结合的人干扰素-γ(HIFN-Gamma)相互作用,但是鼠疫力发病机制中这些相互作用的意义是未知的。在本研究中,我们确定了LCRV和LCRV(68-326)的特异性相互作用在受体结合的HIFN-γ存在下用原发性人胸腺细胞和Jurkat T-白血病细胞参数。尽管HIFN-GAMMA的C末端区域含有LCRV和LCRV(68-326)的高亲和力结合所需的GRA(138-141)位点,但是在HIFN-Gamma同源二聚体中,这些GRA(138-141)靶标仅在将HIFN-γ同型旋转性胸腺细胞或Jurkat T细胞的HIFN-Gamma受体上固定在HIFN-Gamma同源体之后,靶向LCRV或LCRV(68-326)的靶向。 LCRV或LCRV(68-326)对胸腺细胞或Jurkat T细胞对受体结合的HIFN-γ的相互作用引起了两种细胞类型的凋亡,这可以通过加入特异于LEEL32-35的单克隆抗体完全阻塞和Deei203-206 LCRV的网站。 LCRV利用HIFN-GAMMA的能力是阴险的,并且可能占人类瘟疫的严重症状。 (c)2018年elestvier b.v.保留所有权利。

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