The role of T cell receptor signaling thresholds in guiding T cell fate decisions.
The role of T cell receptor signaling thresholds in guiding T cell fate decisions.
复制标题
T 细胞受体信号传导阈值在指导 T 细胞命运决定中的作用。
DOI：
10.1016/j.coi.2015.01.012
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发表时间：
2015
影响因子：
7
通讯作者：
Au-Yeung,Byron
中科院分区：
文献类型：
--
作者：
Zikherman,Julie;Au-Yeung,Byron
亮点累积的TCR信号必须达到T细胞应答的阈值。正反馈回路可以将分级输入转换为开关式数字输出。开关-类似于数字反应。肽亲和力的分辨率是以剂量敏感性为代价的。群体异质性将数字单细胞行为转化为分级输出。经典T细胞受体信号转导已被广泛研究和剖析在细胞系和初级淋巴细胞中。然而，这种信号级联的静态描述未能捕获单个T细胞区分TCR：肽-MHC亲和力，然后随时间整合信号以驱动离散细胞行为（例如胸腺选择、增殖和细胞因子产生）的复杂和动态过程。最近的技术进步使得在单细胞水平上研究复杂的淋巴细胞行为成为可能，并揭示了T细胞如何解释有关抗原亲和力和丰度的信息，以便单独和集体地做出生死细胞命运的决定。
HighlightsAccumulated TCR signaling must reach thresholds for T cell responses.Positive feedback loops can transform graded inputs into switch-like digital output.Sharp signaling thresholds are enforced by switch-like digital responses.Resolution of peptide affinity is imposed at the expense of dose sensitivity.Population heterogeneity transforms digital single cell behavior into graded output.Canonical T cell receptor signal transduction has been extensively studied and dissected in cell lines and primary lymphocytes. However, a static depiction of this signaling cascade fails to capture the complex and dynamic process by which individual T cells discriminate TCR: peptide–MHC affinity, then integrate signals over time to drive discrete cellular behaviors such as thymic selection, proliferation, and cytokine production. Recent technological advances have made it possible to study complex lymphocyte behavior on a single cell level and are revealing how T cells interpret information about affinity and abundance of antigen in order to make life-and-death cell fate decisions individually and collectively.