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Title:Art v 1 IgE epitopes of patients and humanized mice are conformational
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)
Files:URL URL - Source URL, visit https://www.jacionline.org/action/showPdf?pii=S0091-6749%2822%2900701-1
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
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.
Keywords:mugwort pollen allergy, IgE epitope, allergen-specific immunotherapy
Article acceptance date:21.04.2022
Publication date:20.06.2022
Year of publishing:2022
Number of pages:str. 1-11
Numbering:Vol. 150, iss.
PID:20.500.12556/DiRROS-15408 New window
UDC:616-097
ISSN on article:1097-6825
DOI:10.1016/j.jaci.2022.04.031 New window
COBISS.SI-ID:116269571 New window
Note:Soavtorja iz Slovenije: Urška BIdovec-Srojković, Peter Korošec; Nasl. z nasl. zaslona; Opis vira z dne 22. 7. 2022;
Publication date in DiRROS:31.08.2022
Views:512
Downloads:204
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Record is a part of a journal

Title:The journal of allergy and clinical immunology
Shortened title:J. allergy clin. immunol.
Publisher:Elsevier
ISSN:1097-6825
COBISS.SI-ID:3614228 New window

Document is financed by a project

Funder:FWF - Austrian Science Fund
Funding programme:Doktoratskollegs (DKs)
Project number:W 1248
Name:Molecular, cellular and clinical allergology, MCCA

Funder:FWF - Austrian Science Fund
Funding programme:Spezialforschungsbereiche (SFBs)
Project number:F4609

Funder:Other - Other funder or multiple funders
Name:theDANUBE-ARC grant of the country of Lower Austria

Funder:Other - Other funder or multiple funders
Name:grant from WORG Pharmaceuticals

Secondary language

Language:Slovenian
Keywords:alergija za pelod pelina, epitop IgE, specifična imunoterapija


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