A stochastic model of cytotoxic T cell responses
A stochastic model of cytotoxic T cell responses
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DOI：
10.1016/j.jtbi.2003.12.011
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发表时间：
2004-05-21
影响因子：
2
通讯作者：
Perelson, AS
中科院分区：
文献类型：
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作者：
Chao, DL;Davenport, MP;Perelson, AS
我们构建了细胞毒性T淋巴细胞(CTL)对抗原的反应和免疫记忆维持的随机阶段结构模型。该模型遵循病毒感染的动态，以及天然CD8(+)T细胞的刺激、增殖和分化为效应CTL，从而可以消除病毒感染的细胞。该模型能够跟踪多个T细胞克隆的动态，每个克隆都有一个由数字串表示的T细胞受体。MHC-病毒多肽复合体也用字符串表示，字符串匹配规则用于计算T细胞受体与病毒表位的亲和力。相互作用的亲和力也是通过考虑感染细胞表面MHC-病毒多肽的密度来计算的。最后，该模型允许T细胞刺激的概率取决于亲和力，但也纳入了抗原非依赖性程序性增殖反应的概念。我们将该模型与淋巴细胞性脉络膜脑膜炎病毒感染的细胞毒性T细胞反应的实验数据进行了比较。(C)2004爱思唯尔有限公司。保留所有权利。
We have constructed a stochastic stage-structured model of the cytotoxic T lymphocyte (CTL) response to antigen and the maintenance of immunological memory. The model follows the dynamics of a viral infection and the stimulation, proliferation, and differentiation of native CD8(+) T cells into effector CTL, which can eliminate virally infected cells. The model is capable of following the dynamics of multiple T cell clones, each with a T cell receptor represented by a digit string. MHC-viral peptide complexes are also represented by strings and a string match rule is used to compute the affinity of a T cell receptor for a viral epitope. The avidities of interactions are also computed by taking into consideration the density of MHC-viral peptides on the surface of an infected cell. Lastly, the model allows the probability of T cell stimulation to depend on avidity but also incorporates the notion of an antigen-independent programmed proliferative response. We compare the model to experimental data on the cytotoxic T cell response to lymphocytic choriomeningitis virus infections. (C) 2004 Elsevier Ltd. All rights reserved.