TCR 和 CD8 上频繁受到 MHC 分子中嵌入的激动性抗原肽施加的串联力的积累触发 T 细胞内的钙。
Accumulation of serial forces on TCR and CD8 frequently applied by agonist antigenic peptides embedded in MHC molecules triggers calcium in T cells.
机构信息
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332; and.
出版信息
J Immunol. 2014 Jul 1;193(1):68-76. doi: 10.4049/jimmunol.1303436. Epub 2014 Jun 2.
Abstract
T cell activation by Ag is one of the key events in adaptive immunity. It is triggered by interactions of the TCR and coreceptor (CD8 or CD4) with antigenic peptides embedded in MHC (pMHC) molecules expressed on APCs. The mechanism of how signal is initiated remains unclear. In this article, we complement our two-dimensional kinetic analysis of TCR-pMHC-CD8 interaction with concurrent calcium imaging to examine how ligand engagement of TCR with and without the coengagement of CD8 initiates signaling. We found that accumulation of frequently applied forces on the TCR via agonist pMHC triggered calcium, which was further enhanced by CD8 cooperative binding. Prolonging the intermission between sequential force applications impaired calcium signals. Our data support a model where rapid accumulation of serial forces on TCR-pMHC-CD8 bonds triggers calcium in T cells.
摘要
T 细胞被抗原激活是适应性免疫的关键事件之一。它是由 TCR 和共受体（CD8 或 CD4）与 APC 上表达的 MHC（pMHC）分子中嵌入的抗原肽相互作用触发的。信号如何起始的机制尚不清楚。在本文中，我们用钙成像来补充我们对 TCR-pMHC-CD8 相互作用的二维动力学分析，以研究 TCR 与 CD8 共结合以及不共结合时与配体的结合如何引发信号。我们发现，通过激动剂 pMHC 对 TCR 施加频繁的力会触发钙，而 CD8 的协同结合会进一步增强钙。延长连续力施加之间的间隔会损害钙信号。我们的数据支持这样一种模型，即 TCR-pMHC-CD8 键上的连续力的快速积累会触发 T 细胞中的钙。
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