Art v 1 IgE epitopes of patients and humanized mice are conformational

Maja Zabel, Milena Weber, Bernhard Kratzer, Cordula Köhler, Beatrice Jahn-Schmid, Gabriele Gadermaier, Pia Gattinger, Urška Bidovec-Stojkovič, Peter Korošec, Ursula Smole, Gert Wurzinger, Kuan-Wei Chen, Carmen Bunu Panaitescu, Ludger Klimek, Isabel Pablos, Katarzyna Niespodziana, Alina Neunkirchner, Walter Keller, Rudolf Valenta, Winfried F Pickl

Research output: Journal article (peer-reviewed)Journal article

3 Citations (Scopus)

Abstract

BACKGROUND: Worldwide, pollen of the weed mugwort (Artemisiavulgaris) 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.

Original languageEnglish
Pages (from-to)920-930
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume150
Issue number4
Early online date20 Jun 2022
DOIs
Publication statusPublished - Oct 2022

Keywords

  • Allergy
  • Art v 1
  • IgE epitope
  • allergen
  • allergen-specific immunotherapy
  • epitope mapping
  • mugwort pollen allergy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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