二维TCR和pMHC相互作用的动力学决定了T细胞的响应能力
Jun Huang1, Veronika I Zarnitsyna, Baoyu Liu
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Nature
|April 2, 2010
概括
与-MHC (pMHC) 结合的二维T细胞受体 (TCR) 显示出快速的动力学和广泛的亲属性,这对T细胞的反应能力和病原体歧视至关重要. 这些发现挑战了以前的3D分析,并突出了细胞环境的作用.
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:
- T细胞受体 (TCR) 与主要基因相容性复合体 (pMHC) 的相互作用对于区分病原体与自身至关重要.
- 适应性免疫反应取决于这种TCR-pMHC结合,这种结合通过直接的细胞与细胞接触在二维膜上发生.
研究的目的:
- 在二维细胞环境中研究TCR-pMHC结合动力学和亲缘关系.
- 将二维结合参数与传统的三维分析进行比较,并将其与T细胞响应性相关联.
主要方法:
- 利用两种机械分析来测量TCR-pMHC相互作用在一个二维 (2D) 设置.
- 分析了各种pMHC配体的结合动力学 (上速率,下速率) 和亲和力.
主要成果:
- 由快速启动率驱动的高2D TCR-pMHC亲和力,具有比3D分析更广泛的动态范围.
- 与3D相比,观察到显著更快的2D脱离率 (高达8300倍),其中抗体pMHC分离速度最快.
- 发现二维结合参数,特别是快速动力学,与T细胞反应相比,与三维脱离率更好地相关.
结论:
- 细胞环境显著放大TCR-pMHC结合,产生广泛的亲和力和T细胞响应能力所必需的快速动力学.
- 建议T细胞快速取样抗原,并在自我pMHC背景中连续参与agonist pMHCs.
- 2D分析为理解TCR-pMHC相互作用和T细胞激活提供了更准确的模型.
更多相关视频
相关概念视频
Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...


