来自不同B细胞亚群的抗体的多活性是由可变区域的独特序列模式决定的
Maxime Lecerf1, Robin V Lacombe1, Jordan D Dimitrov1
1Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, Université Paris Cité, Paris, France.
Frontiers in immunology
|December 11, 2023
概括
人类抗体结合多个抗原 (多反应性抗体) 显示特定的序列模式. 这些模式因B细胞类型而异,表明免疫反应过程中的进化和治疗性抗体开发的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 抗体多活性,即结合多个抗原的能力,是免疫系统的一个关键特征.
- 了解多重活性的序列决定因素对于抗体工程和治疗开发至关重要.
研究的目的:
- 为了统计分析人类抗体中多重活性的序列相关物.
- 为了研究不同的B细胞类型如何利用不同的序列模式来结合多活性抗原.
- 为了协调有关抗体多活性决定因素的相互矛盾的数据.
主要方法:
- 来自健康的人类B细胞的600个抗体序列的统计分析.
- 在重型和轻型免疫球蛋白链的可变区域中识别序列模式.
- 选择多活性抗体的分子建模.
主要成果:
- 确定了与多重活性相关的关键序列模式:增加了基性/芳香性/水性残留物,减少了酸性残留物,以及更长的CDR L1.
- 证明不同的B细胞种群使用不同的序列模式来实现多重活性.
- 显示抗体可以通过多个分子途径实现抗原结合性.
结论:
- 抗体多活性机制在免疫反应过程中演变,并根据B细胞区的功能进行调整.
- 这些发现为治疗抗体的开发和工程提供了洞察力.
- 调和了关于抗体多活性决定因素的现有文献.
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