T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse

AE Moran, KL Holzapfel, Y Xing… - Journal of Experimental …, 2011 - rupress.org
AE Moran, KL Holzapfel, Y Xing, NR Cunningham, JS Maltzman, J Punt, KA Hogquist
Journal of Experimental Medicine, 2011rupress.org
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 …
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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