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

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