Characterization of allergen-specific T-cell responses in a humanized mouse model relying on a human mugwort-specific T-cell receptor and HLA-DR1 (P6208)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.62-62.3
• Main Authors: Neunkirchner, Alina, Mager, Lukas, Wojta-Stremayr, Daniela, Schmetterer, Klaus, Leb-Reichl, Victoria, Rosloniec, Edward, Ronald, Naumann, Jahn-Schmid, Beatrice, Bohle, Barbara, Pickl, Winfried
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.62.3

While mice expressing an I-Ad restricted murine T-cell receptor (TCR) specific for chicken ovalbumin (Ova) are widely used to mimic allergic diseases induced by aeroallergens in vivo, implications for human allergic diseases remain questionable, since Ova is not a human-relevant aeroallergen. We here created double tg mice expressing a human TCR specific for the major mugwort (Artemisia vulgaris) pollen allergen Art v 1 and HLA-DR1. In tg mice ninety percent of peripheral blood CD4+ T lymphocytes expressed the Art v 1-specific TCR, while CD14+ monocytes and B220+ B lymphocytes revealed HLA-DR1 expression. Splenocytes of tg mice specifically proliferated upon incubation with the human-relevant immuno-dominant Art v 125-36 peptide or whole Art v 1 protein when compared to control mice. In vivo, after allergen-specific sensitization, only tg mice showed enhanced airway-hyperreactivity (AHR) as assessed by methacholine or allergen-specific challenge. Three consecutive exposures to nebulized allergen were found to be sufficient for induction of AHR. The effects on bronchoalveolar lavage fluids, lung histology and specific antibody titers will be described and discussed. Humanized allergy models are amenable to the evaluation of human-relevant allergen formulations or cellular intervention protocols and will thus contribute to the further understanding of allergic diseases and their cure.