αβT细胞受体机械感应的生物物理和结构特征:理解T细胞激活的范式转变
Robert J Mallis1,2,3,4, Kristine N Brazin1,2,3, Jonathan S Duke-Cohan1,2,3
1Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
阿尔法-β T 细胞受体 (TCR) 使用机械力来检测疾病,利用细胞运动的能量. 这种力介导的信号机制是T细胞功能和免疫反应的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
背景情况:
- 阿尔法-β T 细胞 (αβT 细胞) 对于脊椎动物免疫是至关重要的,区分自我与非自我.
- αβT细胞受体 (TCR) 功能非热,利用机械力获得能量.
- 抗原识别涉及αβTCR与-MHC复合体形成捕获键,增强歧视.
研究的目的:
- 阐明机械力在αβTCR信号传递中的作用.
- 解释物理力如何启动T细胞信号级联.
- 为了解αβTCR抗原的识别和特异性提供一个框架.
主要方法:
- 研究了αβTCR对机械负荷的反应.
- 分析了Ig域和CD3子单元的结构转变.
- 假设的信号启动机制涉及结构重组和膜扰动.
主要成果:
- 在强力作用下,αβTCR会发生可逆的结构变化,包括部分展开.
- 这些强力诱导的过渡被假设通过暴露CD3ITAM来启动信号传输.
- 机械传导澄清了αβTCR抗原的识别,特异性和亲和性.
结论:
- 强力介导信号对αβTCR功能和免疫监测至关重要.
- 了解这种机械传导范式可以改善基于T细胞的疗法.
- 未来的研究将专注于原子化机制,性能和T细胞记忆.
更多相关视频
16:10A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
09:53Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
Published on: February 6, 2017
相关概念视频
Tension Response at Adherens Junctions
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
Cell-matrix's Response to Mechanical Forces
Anchoring junctions mechanically attach a cell to the...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
Intracellular Signaling Affects Focal Adhesions
Some...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
