20.500.12556/DiRROS-15408 Art v 1 IgE epitopes of patients and humanized mice are conformational Background: Worldwide, pollen of the weed mugwort (Artemisia vulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and the corresponding HLA have been made. Objective: We sought to characterize IgE epitopes of Art v 1–sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. Methods: Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. Results: Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients’ IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. Conclusions: Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy. mugwort pollen allergy IgE epitope allergen-specific immunotherapy alergija za pelod pelina epitop IgE specifična imunoterapija true false true Angleški jezik Slovenski jezik Neznano 2022-08-31 14:21:20 2022-08-31 14:21:21 2022-09-01 03:34:32 0000-00-00 00:00:00 2022 0 0 Soavtorja iz Slovenije: Urška BIdovec-Srojković, Peter Korošec; Nasl. z nasl. zaslona; Opis vira z dne 22. 7. 2022; str. 1-11 iss. Vol. 150 2022 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 2022-04-21 2022-06-20 616-097 1097-6825 10.1016/j.jaci.2022.04.031 116269571 https://www.jacionline.org/action/showPdf?pii=S0091-6749%2822%2900701-1 1 6fb87329-2927-11ed-b6b8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20365 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0