Generation of the first TCR transgenic mouse with CD4+ T cells recognizing an anti-inflammatory regulatory T cell-inducing Hsp70 peptide

Manon A A Jansen, Martijn J C Van Herwijnen, Peter J S Van Kooten, Aad Hoek, Ruurd Van Der Zee, Willem Van Eden, Femke Broere

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Antigen-specific regulatory T cells (Tregs) directed at self-antigens are difficult to study since suitable specific tools to isolate and characterize these cells are lacking. A T cell receptor (TCR)-transgenic mouse would generate possibilities to study such -antigen-specific T cells. As was shown previously, immunization with the mycobacterial heat shock protein (Hsp) 70-derived peptide B29 and its mouse homologs mB29a and mB29b induced anti-inflammatory responses. Furthermore, B29 induced antigen--specific Tregs in vivo. To study mB29b-specific Tregs, we isolated the TCR from T cell hybridomas generated against mB29b and produced a TCR transgenic mouse that expresses a MHC-class II restricted mB29b-specific TCR. These TCR transgenic CD4(+) T cells were found to cross-react with the B29 epitope as identified with peptide-induced proliferation and IL-2 production. Thus, we have successfully generated a novel mouse model with antigen-specific CD4(+) T cells that recognize self and bacterial Hsp 70-derived peptides. With this novel mouse model, it will be possible to study primary antigen-specific T cells with specificity for a regulatory Hsp70 T cell epitope. This will enable the isolation and characterization CD4(+)CD25(+) Tregs with a proven specificity. This will provide useful knowledge of the induction, activation, and mode of action of Hsp70-specific Tregs, for instance, during experimental arthritis.
    Original languageEnglish
    Article number90
    JournalFrontiers in Immunology
    Volume7
    DOIs
    Publication statusPublished - 9 Mar 2016

    Keywords

    • Autoimmunity
    • Heat shock protein 70
    • Hybridoma
    • Regulatory T cells
    • Transgenic mouse

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