Perspectives for Computer Modeling in the Study of T Cell Activation
Perspectives for Computer Modeling in the Study of T Cell Activation
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DOI：
10.1101/cshperspect.a005538
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发表时间：
2010-06-01
影响因子：
7.2
通讯作者：
Altan-Bonnet, Gregoire
中科院分区：
文献类型：
--
作者：
Coward, Jesse;Germain, Ronald N.;Altan-Bonnet, Gregoire
T细胞受体（TCR）负责区分自身和外源肽，将氨基酸序列的微小差异转化为反应的巨大差异。由于TCR及其配体的巨大变异性，外源肽对T细胞的活化是一个定量过程，依赖于上游信号和下游整合的混合。因此，定量数据和计算模型揭示了这个过程的许多重要方面：配体识别中的分子噪声，T细胞-APC（抗原呈递细胞）相互作用中的空间动力学，TCR装置的分级与全或无决策，肽拮抗和协同作用的机制，以及激活阈值的可调性和鲁棒性。尽管这些研究在形式上各不相同，但它们共同描绘了模型如何塑造并将继续塑造对T细胞免疫生物学的理解。
The T cell receptor (TCR) is responsible for discriminating between self- and foreign-derived peptides, translating minute differences in amino-acid sequence into large differences in response. Because of the great variability in the TCR and its ligands, activation of T cells by foreign peptides is a quantitative process, dependent on a mix of upstream signals and downstream integration. Accordingly, quantitative data and computational models have shed light on many important aspects of this process: molecular noise in ligand recognition, spatial dynamics in T cell-APC (antigen presenting cell) interactions, graded versus all-or-none decision making by the TCR apparatus, mechanisms of peptide antagonism and synergism, and the tunability and robustness of activation thresholds. Though diverse in their formalism, these studies together paint a picture of how modeling has shaped and will continue to shape understanding of T cell immunobiology.