通过含有 LILRB1 的抗体结合疟疾的结构基础
Yiwei Chen1,2, Kai Xu3, Luca Piccoli1
1Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
Nature
|April 1, 2021
概括
研究人员通过结合LILRB1受体发现了针对Plasmodium falciparum RIFINs的新型抗体. 这项研究证明了通过受体域插入生成RIFIN特异性抗体的自然机制,为抗体工程提供了洞察力.
科学领域:
- 免疫学
- 结构生物学
- 寄生虫学
背景情况:
- 菌重复间隔的多家族 (RIFINs) 是感染红细胞表达的表面抗原的变体.
- 之前的研究表明,将LAIR1DNA插入免疫球蛋白基因可以产生RIFIN特异性抗体.
研究的目的:
- 通过检查与RIFINs结合的另一种抑制受体LILRB1来研究受体域插入对抗体生成的一般相关性.
- 识别和描述包含 LILRB1 域的抗体.
主要方法:
- 来自马里捐献者的血检查以识别含有LILRB1抗体的个体.
- 隔离B细胞克隆并分析切换区域中的DNA插入.
- 使用质谱和结合试验来确定与LILRB1结合的RIFIN.
- 确定RIFIN-LILRB1复合体和抗体碎片 (Fabs) 的晶体和冷电子显微镜结构
主要成果:
- 发现了含有 LILRB1 的抗体.
- 在VH-CH1肘部中,B细胞克隆体现了编码LILRB1细胞外域 (D3D4或D3) 的DNA插入.
- 发现一组RIFIN可以结合LILRB1域3 (D3).
- 结构分析显示RIFIN-LILRB1 D3的相互作用模式与RIFIN-LAIR1相似,抗体具有非常规的结构.
结论:
- 通过D3域与LILRB1结合.
- 这项研究提供了一个自然发生的例子,说明将受体域插入VH-CH1肘部可以产生新的RIFIN特异性抗体.
- 这些发现说明了通过受体域插入产生新抗体的一般原则.
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