在Streptococcus pyogenes M蛋白免疫原中保存的3D模式引起了M型交叉反应
Kuei-Chen Wang1, Eziz Kuliyev1, Victor Nizet2
1Department of Chemistry & Biochemistry, University of California, San Diego, California, USA.
The Journal of biological chemistry
|June 30, 2023
概括
杆菌 pyogenes M 蛋白质的差异很大,限制了疫苗的研发. 然而,M蛋白的保存3D模式,它与补充C4b结合蛋白 (C4BP) 结合,可以引起交叉反应抗体,提供一个有前途的疫苗策略.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 疫苗开发 疫苗开发
背景情况:
- 链球菌 pyogenes (链球菌 A) M 蛋白质是关键的毒性因素和抗体标.
- 超过220种类型的M蛋白的抗原变异性,由于类型特异性抗体反应,阻碍了疫苗的疗效.
- 之前的试验显示出与多超变区 (HVR) 免疫原的意外交叉反应性,这表明一种保存的识别机制.
研究的目的:
- 调查M蛋白HVR中保存的3D结构模式,它与补充C4b结合蛋白 (C4BP) 结合,是否可以成为交叉反应抗体反应的基础.
- 为了确定显示这种3D模式的单个M蛋白免疫原是否可以引起对具有相同模式的其他M类型的交叉反应抗体.
主要方法:
- 来自Streptococcus pyogenes M2蛋白质的34氨基酸序列,含有保存的3D图案并保留C4BP结合能力,被合到GCN4卷轴稳定序列中,以创建M2G免疫原体.
- 对M2G的抗体反应被分析为对各种M型的交叉反应.
- 评估了引起的抗体在链球菌A表面识别本地M蛋白的能力,并促进了opsonophagocytic杀死.
主要成果:
- M2G免疫原成功地引起了与共享保存的3D模式的Streptococcus pyogenes M类型的交叉反应抗体.
- 针对M2G产生的抗体与缺乏这种特定3D模式的M类型没有交叉反应.
- 抗体识别了在链杆菌A表面显示的M蛋白,并通过opsonofagocytosis增强了杀死链杆菌A菌株的能力.
结论:
- 与C4BP结合相关的M蛋白HVR中保存的3D结构模式可以作为诱导交叉反应抗体的目标.
- 这种保存模式代表了开发广泛保护性Streptococcus pyogenes疫苗的潜在保存表征.
- 针对这种C4BP结合的3D模式可以克服疫苗设计中M蛋白的类型特异性变异性的局限性.
相关概念视频
00:42Cross-reactivity
31.3K
Overview
31.3K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
01:10Antibody Structure
60.4K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
60.4K