Nonself-Antigens Are the Cognate Specificities of Foxp3+ Regulatory T Cells

Rafal W Pacholczyk, Joanna Kern, Nagendra Singh, Makio Iwashima, Piotr Kraj, Leszek Ignatowicz

Research output: Contribution to journalArticlepeer-review

173 Scopus citations


The majority of regulatory Foxp3+CD4+ T cells naturally arises in the thymus. It has been proposed that T cell receptors (TCRs) on these cells recognize self-MHC class II-peptide complexes with high or higher affinity and that their specificities mirror specificities of autoreactive T cells. Here, we analyzed hundreds of TCRs derived from regulatory or nonregulatory T cells and found little evidence that the former population preferably recognizes self-antigens as agonists. Instead, these cells recognized foreign MHC-peptide complexes as often as nonregulatory T cells. Our results show that high-affinity, autoreactive TCRs are rare on all CD4+ T cells and suggest that selecting self-peptide is different from the peptide that activates the same regulatory T cells in the periphery.

Original languageEnglish (US)
Pages (from-to)493-504
Number of pages12
Issue number3
StatePublished - Sep 21 2007



ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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