早期T细胞抗原受体信号的贝叶斯元模型解释了其纳米级激活模式
Yair Neve-Oz1,2, Eilon Sherman1, Barak Raveh2
1Racah Institute of Physics, The Hebrew University, Jerusalem, Israel.
Frontiers in immunology
|November 11, 2024
概括
贝叶斯元模型揭示了T细胞抗原受体 (TCR) 信号传递的纳米级模式. 这种模式,一种化TCRs的环,源于有限的Lck活性,增强T细胞激活.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞信号传递 细胞信号传递
- 计算生物学 计算生物学
背景情况:
- T细胞对于适应性免疫至关重要,它们对由抗原呈现细胞呈现的抗原做出反应.
- 现有的T细胞抗原受体 (TCR) 信号传递的微观模型缺乏整体视图,阻碍了对早期T细胞激活的理解.
- 超分辨率显微镜数据集为早期免疫突触形成提供了详细的分子洞察力.
研究的目的:
- 通过整合多种现有模型,开发早期T细胞激活的综合模型.
- 阐明早期免疫突触中关键信号分子 (TCR,CD45,Lck) 的时空动态.
- 研究T细胞激活模式背后的分子机制.
主要方法:
- 贝叶斯元模型被用来系统地整合TCR信号的多个部分模型.
- 部分模型由各种超分辨率显微镜数据集提供信息,详细介绍分子组织和动态.
- 综合元模型被用于在各种条件下模拟TCR酸化和T细胞激活.
主要成果:
- 该元模型成功地解释了一种新的纳米尺度模式:在细胞接触外围的化TCRs环,受CD45.5的限制.
- 这种模式归因于Lck分子的有限活性范围,它们调解TCR和CD45.5之间的相互作用.
- 模拟探索了Lck活动范围,TCR-pMHC亲和力,Lck抑制和CD45异型对T细胞激活的影响.
结论:
- 贝叶斯元模型提供了一个可扩展的框架,用于整合各种生物数据来理解复杂的信号系统.
- 确定了纳米级TCR-CD45-Lck组织对于强大的T细胞激活至关重要.
- 这种方法提高了我们对T细胞信号和决策过程的理解.
相关概念视频
T Cell Activation and Clonal Selection
671
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...
671
Diversity of Antigen Receptors
527
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...
527
Assembly of Signaling Complexes
5.7K
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,...
5.7K
B Cell Activation and Differentiation
1.6K
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...
1.6K


