Cooperative enhancement of specificity in a lattice of T cell receptors
Cooperative enhancement of specificity in a lattice of T cell receptors
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DOI：
10.1073/pnas.101113698
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发表时间：
2001-05-08
影响因子：
11.1
通讯作者：
Stark, J
中科院分区：
文献类型：
--
作者：
Chan, C;George, AJT;Stark, J
解释T细胞受体（TCR）的特异性和敏感性的两个最重要的模型是动力学校正模型和串联连接模型。然而，尽管动力学校正为个体TCR提供了一种方法来准确测量它们参与的时间长度并适当地发出信号，但配体解离的随机性质意味着动力学校正模型意味着在高浓度下细胞的反应将是相对非特异性的。最近的配体实验已经揭示了相邻TCR之间的负串扰和正串扰的现象。通过使用蒙特卡罗模拟的TCR晶格，我们集成受体串扰与动力学校对和串行连接模型，发现受体协同性可以提高T细胞的特异性显着在一个非常温和的成本响应的灵敏度。
Two of the most important models to account for the specificity and sensitivity of the T cell receptor (TCR) are the kinetic proofreading and serial ligation models. However, although kinetic proofreading provides a means for individual TCRs to measure accurately the length of time they are engaged and signal appropriately, the stochastic nature of ligand dissociation means the kinetic proofreading model implies that at high concentrations the response of the cell will be relatively nonspecific. Recent ligand experiments have revealed the phenomenon of both negative and positive crosstalk among neighboring TCRs. By using a Monte Carlo simulation of a lattice of TCRs, we integrate receptor crosstalk with the kinetic proofreading and serial ligation models and discover that receptor cooperativity can enhance T cell specificity significantly at a very modest cost to the sensitivity of the response.