Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 6, Pages 1279-1289Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110308
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Funding
- National Institutes of Health [RO1 AI39560, T32 AI007313]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0922653] Funding Source: National Science Foundation
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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.
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