一种病毒免疫酶通过向原型自然杀手细胞受体家族来控制先天免疫力
Oscar A Aguilar1, Richard Berry2, Mir Munir A Rahim3
1Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Cell
|March 25, 2017
概括
研究人员确定了一种来自小鼠细胞大脑病毒的病毒蛋白m12,作为NK1.1受体的难以捉摸的配体. 这一发现揭示了病毒如何操纵NK细胞免疫力,并提供了对宿主-病原体相互作用的见解.
科学领域:
- 免疫学
- 病毒学
- 结构生物学
背景情况:
- 自然杀手 (NK) 细胞对于先天免疫至关重要,通过NK细胞受体 (NKR) 识别配体.
- 关键NKR的NK1.1受体的生理连接体仍然未知.
- 对于先天免疫研究来说,了解NKR-连接物相互作用至关重要.
研究的目的:
- 为了确定NK1.1受体的难以捉摸的生理连接体.
- 阐明病毒配体与NKR-P1受体相互作用的机制.
- 研究这种相互作用在病毒感染期间对NK细胞反应的影响.
主要方法:
- 病毒蛋白的识别和表征.
- 研究NKR-P1受体结合的生物化学测试.
- 结构生物学技术 (例如晶体学) 来确定相互作用机制.
- 使用病毒和宿主遗传修饰的体内研究.
主要成果:
- 鉴定出一种由小鼠细胞巨核病毒 (MCMV) 编码的蛋白质m12,作为NKR- P1 (NK1. 1) 受体的病毒连接体.
- m12直接激活抑制NKR- P1B受体以抑制NK细胞的功能.
- m12还与激活NKR- P1A/ C受体相互作用,从而产生对抗作用.
- 结构分析显示m12与NKR-P1结合的"极地爪"机制.
- 病毒m12和宿主NKR- P1的多态化/消去影响NK细胞体内反应.
结论:
- 病毒蛋白m12是长期寻找的NKR-P1 (NK1.1) 家族的外来配体.
- 这种相互作用在MCMV感染期间调节NK细胞效应器功能.
- 这些发现揭示了病毒免疫逃避的新机制,并突出了宿主-病原体免疫识别的进化平衡.
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