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

Elisa Kieback 1, 2 Ellen Hilgenberg 3 Ulrik Stervbo 3 Vicky Lampropoulou 3 Ping Shen 3 Mario Bunse 2 Yarua Jaimes 3 Pierre Boudinot 4 Andreas Radbruch 3 Uwe Klemm 5 Anja A. Kühl 6 Roland Liblau 7 Nadine Hoevelmeyer 8 Stephen M. Anderton 9 Wolfgang Uckert 1, 2 Simon Fillatreau 10, 11, 12, 13, 3
1 Institute of Biology
2 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
3 Leibniz Association
4 VIM (UR 0892) - Unité de recherche Virologie et Immunologie Moléculaires
5 MPIIB - Max Planck Institute for Infection Biology
6 Institute of Pathology
7 UT3 - Université Toulouse III - Paul Sabatier
8 Institute for Molecular Medicine
9 University of Edinburgh
10 Faculté de Médecine
11 USPC - Université Sorbonne Paris Cité (COMUE)
12 CHU Necker - Enfants Malades [AP-HP]
13 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
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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INRAE | UNIV-TLSE3 | INRA | CNRS | UNIV-PARIS5 | UP-SANTE | INSERM | USPC | UNIV-PARIS-SACLAY | UNIV-PARIS | AFRIQ | GS-HEALTH-DRUG-SCIENCES

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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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