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

Immunity. 2007 Sep;27(3):493-504. doi: 10.1016/j.immuni.2007.07.019.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology
  • Autoantigens / immunology*
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Molecular Sequence Data
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Self Tolerance / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Wasting Syndrome / immunology


  • Autoantigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell