完全组装的 γδ T 细胞抗原受体的结构
Benjamin S Gully1, João Ferreira Fernandes2,3, Sachith D Gunasinghe1
1Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Nature
|August 15, 2024
概括
确定了玛- 三角形T细胞受体 (TCR) 的结构,显示了CD3亚单元的保存组织,但与α-β TCR相比具有独特的灵活性. 这种结构性可塑性使得马-三角 TCR 能够识别不同的配体,同时保持信号传输能力.
科学领域:
- 免疫学
- 结构生物学
- 分子生物学
背景情况:
- 对于适应性免疫至关重要的T细胞存在于αβ和γδ系,由它们的T细胞受体 (TCR) 区分开来.
- 虽然αβ T 细胞受体的结构是很好的特征,但 γδ T 细胞受体的结构仍然是未知的.
- 已知 γδ T 细胞受体比αβ T 细胞受体识别了更广泛的配体,这表明其具有独特的结构性质.
研究的目的:
- 确定人类 γδ T 细胞受体综合体的三维结构.
- 将 γδ TCR 的结构组织和灵活性与已知的 αβ TCR 结构进行比较.
- 了解 γδ TCR 结构与其多样化的联结能力和信号功能之间的关系.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 可视化组装的人类Vγ8Vδ3 TCR- CD3复合体.
- 该复合物与MR1和抗CD3ε抗体片段一起研究.
- 结构分析侧重于TCR变量域和保存的CD3子单元的排列和相互作用.
主要成果:
- 这项研究确定了人类 γδ TCR- CD3 综合体的结构,揭示了与αβ TCRs相似的保存 CD3 子单元排列.
- 与刚性αβ TCR不同,由于其跨膜螺旋连接,γδ TCR表现出显著的结构异质性.
- 修改 γδ TCR 以类似于αβ TCR 结构增强了信号,表明了连接物多样性和信号效率之间的权衡.
结论:
- γδ TCR 结构表现出显著的可塑性,适应其灵活性以适应多样化的联体识别.
- 这种结构性适应性是一个关键的进化特征,使得 γδ T 细胞能够发挥不同的免疫作用.
- 这些发现重新定义了TCR作为一种多功能受体,能够通过刚性和灵活的形状发出信号.
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