Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity


  • E. Kieback
  • E. Hilgenberg
  • U. Stervbo
  • V. Lampropoulou
  • P. Shen
  • M. Bunse
  • Y. Jaimes
  • P. Boudinot
  • A. Radbruch
  • U. Klemm
  • A.A. Kühl
  • R. Liblau
  • N. Hoevelmeyer
  • S.M. Anderton
  • W. Uckert
  • S. Fillatreau


  • Immunity


  • Immunity 44 (5): 1114-1126


  • Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expression of T cell receptor of higher functional avidity for self-antigen by Treg cells than Tconv cells, a difference subsequently essential for the control of autoimmunity. Our study documents how self-antigens define the repertoire of thymus-derived Treg cells to subsequently endow this cell type with the capacity to undermine autoimmune attack.