一种细胞质简单疹病毒蛋白质抑制了对CD8+ T淋巴细胞的抗原呈现
I A York1, C Roop, D W Andrews
1Department of Pathology, McMaster University Hamilton, Ontario, Canada.
Cell
|May 20, 1994
概括
简单疹病毒 (HSV) 通过阻断细胞毒性T淋巴细胞 (CTL) 识别来逃避免疫检测. 病毒蛋白ICP47阻止感染细胞在MHC I类分子上呈现病毒,从而抑制CTL介导的溶解.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 简单疹病毒 (HSV) 感染人类纤维细胞,导致对CD8+细胞毒性T淋巴细胞 (CTLs) 的抵抗.
- 通常情况下,CTLs会在受感染细胞表面上识别主要基因相容性复合体 (MHC) I类蛋白所呈现的病毒.
- 感染HSV会破坏这种识别过程,使病毒能够逃避免疫监测.
研究的目的:
- 研究HSV感染细胞逃避CD8+CTL介导溶解的机制.
- 为了确定负责阻断病毒抗原呈现的病毒成分.
- 了解HSV感染如何影响宿主免疫反应.
主要方法:
- 人体纤维细胞感染HSV.
- 对MHC I类蛋白位址和感染细胞内的载荷进行分析.
- 对受感染细胞的CD8+ CTL介导溶解的评估.
- 研究HSV直接早期蛋白质ICP47.7.的作用.
主要成果:
- 在HSV感染后3小时内,MHC I类蛋白质复合物被保留在内质网膜/cis Golgi中.
- 这些保留的MHC I类复合体缺乏抗原,使它们无法被CTL检测.
- HSV蛋白 ICP47既必要又足以阻断MHC I类运输,并抑制CD8+ CTL溶解.
- ICP47似乎干扰了的产生,稳定或转移到ER/cis Golgi.
结论:
- HSV利用ICP47蛋白来积极逃避CD8+ T淋巴细胞的检测.
- 这种逃避机制涉及MHC I类复合物的保留在ER/cis Golgi中,防止抗原呈现.
- HSV 抑制 CD8+ CTL 响应的能力可能解释了在体内观察到的 CD4+ HSV 特定 CTL 的主导地位.
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