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

Amy E. Moran, Keli L. Holzapfel, Yan Xing, Nicole R. Cunningham, Jonathan S. Maltzman, Jennifer Punt, Kristin A. Hogquist

Research output: Contribution to journalArticle

505 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1279-1289
Number of pages11
JournalJournal of Experimental Medicine
Volume208
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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