Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414, USA.
J Exp Med. 2011 Jun 6;208(6):1279-89. doi: 10.1084/jem.20110308. Epub 2011 May 23.
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 (T(reg) cells) and invariant NKT cells (iNKT cells) perceived stronger TCR signals than conventional T cells during development. However, although T(reg) cells continued to perceive strong TCR signals in the periphery, iNKT cells did not. Finally, we show that T(reg) cell progenitors compete for recognition of rare stimulatory TCR self-ligands.
抗原受体与不同亲和力的自身配体结合的能力对于淋巴细胞的发育至关重要。为了进一步探讨这一概念，我们生成了表达 GFP 的转基因小鼠，GFP 由即刻早期基因 Nr4a1（Nur77）基因座表达。抗原受体刺激可上调 GFP 在淋巴细胞中的表达，但炎症刺激物不能上调。在 T 细胞中，GFP 在阳性选择过程中诱导表达，需要主要组织相容性复合物维持，并与 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，我们表明调节性 T 细胞（Treg 细胞）和不变自然杀伤 T 细胞（iNKT 细胞）在发育过程中感知到比常规 T 细胞更强的 TCR 信号。然而，尽管 Treg 细胞在周围组织中继续感知到强烈的 TCR 信号，但 iNKT 细胞却没有。最后，我们表明 Treg 细胞前体竞争识别罕见的刺激性 TCR 自身配体。
