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EMBO J. 2018 Feb 1;37(3):398-412. doi: 10.15252/embj.201796881. Epub 2017 Dec 20.

Regulatory T cells constrain the TCR repertoire of antigen-stimulated conventional CD4 T cells.

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Laboratoire d'Immunobiologie, Université Libre de Bruxelles (ULB), Gosselies, Belgium.
DIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB), Gosselies, Belgium.
Laboratories of Image, Signal processing & Acoustics Université Libre de Bruxelles (ULB), Brussels, Belgium.
Retroviral Immunology, The Francis Crick Institute, London, UK.
Department of Medicine Faculty of Medicine, Imperial College London London, UK.
Laboratoire d'Immunobiologie, Université Libre de Bruxelles (ULB), Gosselies, Belgium


To analyze the potential role of Tregs in controlling the TCR repertoire breadth to a non-self-antigen, a TCRβ transgenic mouse model (EF4.1) expressing a limited, yet polyclonal naïve T-cell repertoire was used. The response of EF4.1 mice to an I-Ab-associated epitope of the F-MuLV envelope protein is dominated by clones expressing a Vα2 gene segment, thus allowing a comprehensive analysis of the TCRα repertoire in a relatively large cohort of mice. Control and Treg-depleted EF4.1 mice were immunized, and the extent of the Vα2-bearing, antigen-specific TCR repertoire was characterized by high-throughput sequencing and spectratyping analysis. In addition to increased clonal expansion and acquisition of effector functions, Treg depletion led to the expression of a more diverse TCR repertoire comprising several private clonotypes rarely observed in control mice or in the pre-immune repertoire. Injection of anti-CD86 antibodies in vivo led to a strong reduction in TCR diversity, suggesting that Tregs may influence TCR repertoire diversity by modulating costimulatory molecule availability. Collectively, these studies illustrate an additional mechanism whereby Tregs control the immune response to non-self-antigens.


CD4+ T‐cell lymphocytes; TCR repertoire analysis; regulatory T cells

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