Generation of the First TCR Transgenic Mouse with CD4(+) T Cells Recognizing an Anti-inflammatory Regulatory T Cell-Inducing Hsp70 Peptide

• Published in: Frontiers in immunology Vol. 7; p. 90
• Main Authors: Jansen, Manon A A, van Herwijnen, Martijn J C, van Kooten, Peter J S, Hoek, Aad, van der Zee, Ruurd, van Eden, Willem, Broere, Femke
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 09.03.2016
• Subjects: Autoimmunity; heat shock protein 70; hybridoma; Immunology; regulatory T cells; Transgenic mouse; regulatory T cells; heat shock protein 70; hybridoma; autoimmunity; transgenic mouse
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2016.00090

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.