Epitopes described in "Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure."

Article Authors:Philipp Neudecker; Katrin Lehmann; Jörg Nerkamp; Tanja Haase; Andrea Wangorsch; Kay Fötisch; Silke Hoffmann; Paul Rösch; Stefan Vieths; Stephan Scheurer
Article Title:Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.
Reference Detail
Reference ID:1005426
Abstract:Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy.
Affiliations:Lehrstuhl für Biopolymere, Universitaet Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany. philipp.neudecker@uni-bayreuth.de.
Reference Type:Literature
PubMed ID:12943529
Journal:Biochem J
Journal Volume:376
Article Pages:97-107
Journal ISSN:0264-6021
Article Chemical List:Allergens;Antibodies, Monoclonal;Antigens, Plant;Api g 1 protein, Apium graveolens;Epitopes;Plant Proteins;Pru av 1 allergen, Prunus avium;Recombinant Proteins;Immunoglobulin E
Article MeSH List:Allergens(chemistry; genetics; immunology); Amino Acid Sequence; Animals; Antibodies, Monoclonal(immunology); Antigens, Plant; DNA Mutational Analysis; Epitopes(chemistry; genetics; immunology); Food Hypersensitivity(immunology); Humans; Immunoglobulin E(immunology); Mice; Models, Molecular; Molecular Sequence Data; Plant Proteins(chemistry; genetics; immunology); Protein Conformation; Prunus(immunology); Recombinant Proteins(chemistry; immunology; metabolism); Sequence Alignment
Curation Last Updated:2015-06-05 00:58:12