T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens.
T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens.
复制标题
T 细胞整合局部和全局线索来区分结构相似的抗原。
DOI：
10.1016/j.celrep.2015.04.051
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发表时间：
2015
期刊：
影响因子：
8.8
通讯作者：
Altan-Bonnet,Grégoire
中科院分区：
文献类型：
--
作者：
Voisinne,Guillaume;Nixon,BrianaG;Melbinger,Anna;Gasteiger,Georg;Vergassola,Massimo;Altan-Bonnet,Grégoire
T淋巴细胞区分结构相关抗原的能力归因于T细胞受体独特的信号传导特性。然而，最近的研究表明，这种歧视过程的输出是由环境线索。在这里，我们展示了如何IL-2细胞因子，共同产生的强烈激活的T细胞克隆，可以诱导较弱的T细胞克隆增殖。我们确定PI 3 K通路对于整合抗原和细胞因子应答以及控制细胞周期进入至关重要。我们建立了一个混合的随机/确定性计算模型，占这种信号协同作用，并定量地演示了T细胞如何根据环境细胞因子的线索调整他们的细胞周期进入。我们的研究结果表明，T细胞的抗原识别不仅仅是一种内在的细胞特性，而是多种线索整合的产物，包括局部线索，如抗原的质量和数量，全球的炎症细胞因子的细胞外浓度。
T lymphocytes' ability to discriminate between structurally related antigens has been attributed to the unique signaling properties of the T cell receptor. However, recent studies have suggested that the output of this discrimination process is conditioned by environmental cues. Here, we demonstrate how the IL-2 cytokine, collectively generated by strongly activated T cell clones, can induce weaker T cell clones to proliferate. We identify the PI3K pathway as being critical for integrating the antigen and cytokine responses and for controlling cell-cycle entry. We build a hybrid stochastic/deterministic computational model that accounts for such signal synergism and demonstrates quantitatively how T cells tune their cell-cycle entry according to environmental cytokine cues. Our findings indicate that antigen discrimination by T cells is not solely an intrinsic cellular property but rather a product of integration of multiple cues, including local cues such as antigen quality and quantity, to global ones like the extracellular concentration of inflammatory cytokines.