A stochastic T cell response criterion.
A stochastic T cell response criterion.
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DOI：
10.1098/rsif.2012.0205
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发表时间：
2012-11-07
期刊：
影响因子：
--
通讯作者：
Molina-París C
中科院分区：
文献类型：
--
作者：
Currie J;Castro M;Lythe G;Palmer E;Molina-París C
适应性免疫系统依赖于不同的细胞类型来提供快速和协调的反应，其特征在于识别病原性挑战、广泛的细胞增殖和分化以及死亡。T细胞是适应性免疫细胞库的一个子集，其通过其膜上的专门受体识别抗原呈递细胞表面上表达的免疫原性肽。T细胞受体与配体的结合决定了T细胞在T细胞寿命期间不同时间和位置的T细胞应答。目前的实验证据提供了以下支持：（i）需要足够长的受体-配体接合来启动导致生产性信号转导的T细胞信号传导级联，以及（ii）计数装置在T细胞中起作用以允许信号积累、解码和翻译成生物反应。根据这些结果，我们用数学模型探索了与T细胞反应相关的时间尺度。我们考虑两种不同的标准：随机标准（使N个受体-配体复合物结合至少停留时间τ所需的平均时间）和基于平衡的标准（达到受体-配体复合物阈值数量N的时间）。我们已经应用数学模型的背景下，胸腺阴性选择和最近的二维实验在以前的实验。我们的研究结果表明，随机标准提供了支持的胸腺亲和力阈值假设，而平衡一个没有，并同意与配体层次实验建立胸腺阴性选择。
The adaptive immune system relies on different cell types to provide fast and coordinated responses, characterized by recognition of pathogenic challenge, extensive cellular proliferation and differentiation, as well as death. T cells are a subset of the adaptive immune cellular pool that recognize immunogenic peptides expressed on the surface of antigen-presenting cells by means of specialized receptors on their membrane. T cell receptor binding to ligand determines T cell responses at different times and locations during the life of a T cell. Current experimental evidence provides support to the following: (i) sufficiently long receptor–ligand engagements are required to initiate the T cell signalling cascade that results in productive signal transduction and (ii) counting devices are at work in T cells to allow signal accumulation, decoding and translation into biological responses. In the light of these results, we explore, with mathematical models, the timescales associated with T cell responses. We consider two different criteria: a stochastic one (the mean time it takes to have had N receptor–ligand complexes bound for at least a dwell time, τ, each) and one based on equilibrium (the time to reach a threshold number N of receptor–ligand complexes). We have applied mathematical models to previous experiments in the context of thymic negative selection and to recent two-dimensional experiments. Our results indicate that the stochastic criterion provides support to the thymic affinity threshold hypothesis, whereas the equilibrium one does not, and agrees with the ligand hierarchy experimentally established for thymic negative selection.
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影响因子：
3.3
作者：
Drews, TO;Katsoulakis, MA;Tsapatsis, M
通讯作者：
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DOI：
10.1073/pnas.1000966107
发表时间：
2010-05-11
影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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