| Title: | Art v 1 IgE epitopes of patients and humanized mice are conformational |
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| Authors: | ID Zabel, Maja (Author)
ID Weber, Milena (Author)
ID Kratzer, Bernhard (Author)
ID Köhler, Cordula (Author)
ID Jahn-Schmid, Beatrice (Author)
ID Gadermaier, Gabriele (Author)
ID Gattinger, Pia (Author)
ID Bidovec, Urška, Klinika Golnik (Author)
ID Korošec, Peter, Klinika Golnik (Author)
ID Smole, Ursula (Author)
ID Valenta, Rudolf (Author)
ID Pickl, Winfried F. (Author) |
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| Files: |  URL - Source URL, visit https://www.jacionline.org/action/showPdf?pii=S0091-6749%2822%2900701-1
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
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| Abstract: | 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. |
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| Keywords: | mugwort pollen allergy, IgE epitope, allergen-specific immunotherapy |
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| Article acceptance date: | 21.04.2022 |
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| Publication date: | 20.06.2022 |
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| Year of publishing: | 2022 |
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| Number of pages: | str. 1-11 |
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| Numbering: | Vol. 150, iss. |
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| PID: | 20.500.12556/DiRROS-15408  |
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| UDC: | 616-097 |
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| ISSN on article: | 1097-6825 |
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| DOI: | 10.1016/j.jaci.2022.04.031 |
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| COBISS.SI-ID: | 116269571 |
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| Note: | Soavtorja iz Slovenije: Urška BIdovec-Srojković, Peter Korošec;
Nasl. z nasl. zaslona;
Opis vira z dne 22. 7. 2022;
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| Publication date in DiRROS: | 31.08.2022 |
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| Views: | 947 |
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| Downloads: | 395 |
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