T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse.
T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse.
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DOI：
10.1084/jem.20110308
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发表时间：
2011-06-06
期刊：
影响因子：
--
通讯作者：
Hogquist KA
中科院分区：
文献类型：
--
作者：
Moran AE;Holzapfel KL;Xing Y;Cunningham NR;Maltzman JS;Punt J;Hogquist KA
Nur77 报告小鼠的产生用于证明常规和非常规 T 细胞亚群的胸腺选择和外周维持期间的 TCR 信号强度，并为研究体内抗原受体激活提供了一种新工具。抗原受体以不同的亲和力结合自身配体的能力对于淋巴细胞的发育至关重要。为了进一步探索这个概念，我们从立即早期基因 Nr4a1 (Nur77) 基因座产生了表达 GFP 的转基因小鼠。淋巴细胞中的 GFP 通过抗原受体刺激而上调，但不通过炎症刺激上调。在 T 细胞中，GFP 在正选择过程中被诱导，需要主要的组织相容性复合物来维持，并且与 T 细胞受体 (TCR) 刺激的强度直接相关。因此，我们的结果定义了一种研究体内抗原受体激活的新工具。使用该模型，我们发现调节性 T 细胞（Treg 细胞）和不变 NKT 细胞（iNKT 细胞）在发育过程中感知到的 TCR 信号比传统 T 细胞更强。然而，尽管 Treg 细胞继续感知到外周的强 TCR 信号，但 iNKT 细胞却没有。最后，我们证明 Treg 细胞祖细胞竞争识别罕见的刺激性 TCR 自配体。
Generation of a Nur77 reporter mouse is used to demonstrate TCR signal strength during thymic selection and peripheral maintenance of conventional and nonconventional T cell subsets and presents a novel tool for studying antigen receptor activation in vivo. The ability of antigen receptors to engage self-ligands with varying affinity is crucial for lymphocyte development. To further explore this concept, we generated transgenic mice expressing GFP from the immediate early gene Nr4a1 (Nur77) locus. GFP was up-regulated in lymphocytes by antigen receptor stimulation but not by inflammatory stimuli. In T cells, GFP was induced during positive selection, required major histocompatibility complex for maintenance, and directly correlated with the strength of T cell receptor (TCR) stimulus. Thus, our results define a novel tool for studying antigen receptor activation in vivo. Using this model, we show that regulatory T cells (Treg cells) and invariant NKT cells (iNKT cells) perceived stronger TCR signals than conventional T cells during development. However, although Treg cells continued to perceive strong TCR signals in the periphery, iNKT cells did not. Finally, we show that Treg cell progenitors compete for recognition of rare stimulatory TCR self-ligands.
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影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
64.8
作者：
Daniels, Mark A.;Teixeiro, Emma;Palmer, Ed
通讯作者：
Palmer, Ed
影响因子：
4.4
作者：
Burchill, MA;Goetz, CA;Farrar, MA
通讯作者：
Farrar, MA
DOI：
10.1084/jem.20050456
发表时间：
2005-08-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Benlagha K;Wei DG;Veiga J;Teyton L;Bendelac A
通讯作者：
Bendelac A