Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors

Immunity. 2004 Aug;21(2):267-77. doi: 10.1016/j.immuni.2004.07.009.


Naturally arising CD25+ CD4+ regulatory T cells (TR) play an important role in the prevention of autoimmunity. TCR specificity is thought to play a critical role in TR development and function, but the repertoire and specificity of TR TCRs remain largely unknown. We find by sequencing of TRAV14 (Valpha2) TCRalpha chains associated with a transgenic TCRbeta chain that the TRand CD25- CD4+ TCR repertoires are similarly diverse, yet only partially overlapping. Retroviral expression of TCRalpha genes in TCR transgenic RAG-deficient T cells revealed that a high frequency of TCRs derived from CD25+ but not CD25- CD4+ T cells confers the ability to rapidly expand upon transfer into a lymphopenic host. Thus, these data show that a large proportion of naturally arising TR have substantially more efficient interactions with MHC class II bound peptides from the peripheral self than CD25- T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Autoantigens / immunology
  • Autoimmunity / immunology
  • Autoimmunity / physiology
  • CD4-Positive T-Lymphocytes / immunology*
  • Mice
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / immunology*
  • Self Tolerance / immunology*
  • Self Tolerance / physiology
  • Spleen / cytology
  • Spleen / immunology


  • Autoantigens
  • Peptides
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2