TCRαβ的不对称框架运动控制了负载依赖的区别
Ana C Chang-Gonzalez1, Robert J Mallis2,3,4, Matthew J Lang5,6
1Department of Biomedical Engineering, Texas A&M University, College Station, United States.
eLife
|January 3, 2024
概括
机械力影响T细胞受体 (TCR) 和-MHC相互作用. 模拟显示了不对称的TCR链运动和对激动剂的负载依赖稳定,有助于歧视.
科学领域:
- 免疫学 免疫学 免疫学
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- 机械力对T细胞受体 (TCR) 和-MHC相互作用起始T细胞激活至关重要.
- 机械力量影响TCR-pMHC结合和T细胞反应的确切机制尚不完全理解.
研究的目的:
- 研究机械力在TCR-pMHC复杂动力学和T细胞激活中的作用.
- 阐明在不同机械负载下由TCRs进行基歧视的分子机制.
主要方法:
- 采用全原子分子动力学模拟来研究A6 TCR与HLA-A*02:01复合,呈现agonist和antagonist.
- 模拟在不同的机械扩展下进行,以模拟应用于负载的模拟,分析侧重于链际运动和接口接触.
主要成果:
- TCRα和β链表现出不对称的运动,显著影响TCR-pMHC接口,特别是感应CDR3循环.
- TCR-pMHC复合体表现出与激动性的负载依赖稳定,而对抗性导致不稳定.
- 涉及Cβ FG循环删除突变和in silico突变的模拟证实了关于机械反应和分辨的发现.
结论:
- 域间运动,波动力和界面接触共同决定了TCR-pMHC复合体的机械反应.
- 这些因素对于TCR来说是必不可少的,以实现精细的歧视,解决激素和对抗体复合物的晶体结构之间的差异.
关键词:
这种T细胞受体是T细胞受体.捕获债券的捕获债券是什么免疫学 免疫学 免疫学这是一种炎症炎症炎症炎症.主要的组织相容性复杂.机械生物学 机械生物学分子生物物理学分子生物物理学分子动力学分子动力学没有,没有,没有.结构生物学结构生物学更多相关视频
相关概念视频
T Cell Activation and Clonal Selection
740
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...
740
Diversity of Antigen Receptors
592
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...
592
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
B Cell Activation and Differentiation
1.7K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.7K
Assembly of Signaling Complexes
5.8K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.8K
Antigens Involved in Adaptive Immunity
498
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
498


