Abstract: The authors use the strategy of kinetic proofreading model to simulate the process of T-cell receptor (TCR) activation and phosphorylation, and modify the original kinetic proofrading model to explain the multi-phosphorylation process of T-cell receptors as proofreading steps which can amplify the tiny difference in the peptide-TCR binding affinity. The new model expands the previous kinetic proofreading models, and removes the two important assumptions in those models. One is that the dephosphorylation rate constant β is assumed to be very large; the other is that the kinetic mechanism of multi-phosphorylation is sequential phosphorylation mechanism. Based on the more general model, besides the specificity of T cell activation, the results successfully interpret other important characteristics of T cell activation, such as the sensitivity and transition time of activation.

Key words: T cell receptor, kinetic proofreading model, multisite phosphorylation, signal transduction pathway, biochemical reaction network

摘要： 对免疫系统T细胞受体结合外源多肽段后诱导的一系列受体磷酸化反应过程进行了系统的理论模拟。T细胞受体对于不同外源分子产生敏感而特异的反应, 可以由动力学校验模型进行解释。拓展了早期的动力学校验模型, 放宽和改进了原有模型对去磷酸化速率和以固定顺序进行受体磷酸化这两方面的假设, 得到了更一般的反应网络模型, 从数学模拟角度很好的满足和解释了生理上T细胞所表现出的对外源分子识别的敏感性、特异性和激活时间短等重要性质。

关键词: T细胞受体, 动力学校验模型, 多位点磷酸化, 信号转导通路, 生化反应网络