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

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.

• Authors: 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
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 150 Issue 4 Pg. 920-930 (10 2022) ISSN: 1097-6825 [Electronic] United States
• PMID: 35738928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Allergens
• Amino Acids
• Antigens, Plant
• Epitopes, T-Lymphocyte
• Immune Sera
• Immunoglobulin G
• Peptides
• Plant Proteins
• Immunoglobulin E

Topics

• Allergens
• Amino Acids
• Animals
• Antigens, Plant
• Artemisia (chemistry)
• Epitopes, T-Lymphocyte
• Humans
• Hypersensitivity
• Immune Sera
• Immunoglobulin E
• Immunoglobulin G
• Mice
• Peptides
• Plant Proteins
• Rabbits