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

Abstract : 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.
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https://hal.inrae.fr/hal-02637633
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Submitted on : Wednesday, May 27, 2020 - 11:39:10 PM
Last modification on : Tuesday, April 5, 2022 - 11:38:02 AM

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Elisa Kieback, Ellen Hilgenberg, Ulrik Stervbo, Vicky Lampropoulou, Ping Shen, et al.. Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity. Immunity, Elsevier, 2016, 44 (5), pp.1114-1126. ⟨10.1016/j.immuni.2016.04.018⟩. ⟨hal-02637633⟩

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