Quorum sensing allows T cells to discriminate between self and nonself
Quorum sensing allows T cells to discriminate between self and nonself
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DOI：
10.1073/pnas.1222467110
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发表时间：
2013-07-16
影响因子：
11.1
通讯作者：
Chakraborty, Arup K.
中科院分区：
文献类型：
--
作者：
Butler, Thomas Charles;Kardar, Mehran;Chakraborty, Arup K.
T 细胞通过识别来自受感染细胞表面的致病蛋白的肽来协调病原体特异性的适应性免疫反应。宿主细胞还展示来自宿主自身蛋白质的肽片段。错误地将源自人体自身蛋白质组的肽识别为致病肽可能会导致自身免疫性疾病。为了最大限度地减少自身反应性，胸腺中对自身肽做出反应的未成熟 T 细胞通过称为负选择的过程被删除。然而，阴性选择并不完美，自身反应性 T 细胞存在于健康个体中。为了了解如何在不丧失对病原体反应能力的情况下避免自身免疫，我们开发了一种 T 细胞训练和反应模型。我们的模型表明，T 细胞能够可靠地对感染做出反应并避免自身免疫，因为决定生物学结果的是 T 细胞群体做出的集体决策，而不是单个 T 细胞的反应。该理论在质量上与实验数据一致，并产生了胸腺选择足以抑制自身免疫的标准。
T cells orchestrate pathogen-specific adaptive immune responses by identifying peptides derived from pathogenic proteins that are displayed on the surface of infected cells. Host cells also display peptide fragments from the host's own proteins. Incorrectly identifying peptides derived from the body's own proteome as pathogenic can result in autoimmune disease. To minimize autoreactivity, immature T cells that respond to self-peptides are deleted in the thymus by a process called negative selection. However, negative selection is imperfect, and autoreactive T cells exist in healthy individuals. To understand how autoimmunity is yet avoided, without loss of responsiveness to pathogens, we have developed a model of T-cell training and response. Our model shows that T cells reliably respond to infection and avoid autoimmunity because collective decisions made by the T-cell population, rather than the responses of individual T cells, determine biological outcomes. The theory is qualitatively consistent with experimental data and yields a criterion for thymic selection to be adequate for suppressing autoimmunity.