通过T细胞抗原受体激活的T细胞中信号复杂纳米结构的异质性
Valarie A Barr1, Juan Piao2, Lakshmi Balagopalan1
1Laboratory of Cellular & Molecular Biology, Building 37 Room 2066, 37 Convent Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-4256, USA.
概括
T细胞激活涉及T细胞受体 (TCR) 信号复合体. 新的显微镜揭示了这些复合体内的蛋白质组织,显示T细胞中具有灵活的纳米组织的动态结构.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- T细胞受体 (TCR) 的激活启动了适应性免疫.
- 了解TCR信号复合体的纳米组织是至关重要的,但具有挑战性.
- 以前的单分子定位显微镜研究缺乏对蛋白质排列的全面了解.
研究的目的:
- 在激活的T细胞信号复合体内可视化多种蛋白质的纳米级组织.
- 改进刺激T细胞中分子位置的统计分析.
- 阐明基于TCR的信号组件的结构动态.
主要方法:
- 使用多重复合抗体大小有限的直接随机光学重建显微镜 (madSTORM).
- 在激活的Jurkat T细胞中可视化六种不同蛋白质的单个分子.
- 开发了新的方法来定义感兴趣的区域和分子分布的统计分析.
主要成果:
- 蛋白质纳米级组织主要集中在密集的基于TCR的信号复合体的区域.
- 一些信号复杂区域还含有随机分布的分子.
- 在激活时观察到T细胞纳米结构的显著变化.
结论:
- TCR信号复合体表现出灵活,动态和可变的纳米结构.
- 这些结构很可能是由许多蛋白质之间的弱相互作用形成的.
- 这些发现为免疫反应期间T细胞纳米结构提供了更清晰的图像.
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