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Regulatory T cells constrain the TCR repertoire of antigen‐stimulated conventional CD 4 T cells
Author(s) -
Fontaine Martina,
Vogel Isabel,
Van Eycke YvesRémi,
Galuppo Adrien,
Ajouaou Yousra,
Decaestecker Christine,
Kassiotis George,
Moser Muriel,
Leo Oberdan
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201796881
Subject(s) - t cell receptor , repertoire , antigen , epitope , biology , immune system , immunology , major histocompatibility complex , polyclonal antibodies , microbiology and biotechnology , t cell , physics , acoustics
To analyze the potential role of Tregs in controlling the TCR repertoire breadth to a non‐self‐antigen, a TCR β transgenic mouse model ( EF 4.1) expressing a limited, yet polyclonal naïve T‐cell repertoire was used. The response of EF 4.1 mice to an I‐Ab‐associated epitope of the F‐Mu LV envelope protein is dominated by clones expressing a Vα2 gene segment, thus allowing a comprehensive analysis of the TCR α repertoire in a relatively large cohort of mice. Control and Treg‐depleted EF 4.1 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‐ CD 86 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.