Protein unfolding strongly modulates the allergenicity and immunogenicity of Pru p 3, the major peach allergen

Masako Toda, Gerald Reese, Gabriele Gadermaier, Veronique Schulten, Iris Lauer, Matthias Egger, Peter Briza, Stefanie Randow, Sonja Wolfheimer, Valencia Kigongo, Maria Del Mar San Miguel Moncin, Kay Fötisch, Barbara Bohle, Stefan Vieths, Stephan Scheurer

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Background: Allergen-specific immunotherapy for food allergies, including peach allergy, has not been established. Use of allergens with reduced allergenic potential and preserved immunogenicity could improve the safety and efficacy of allergen-specific immunotherapy. Objective: We sought to create a hypoallergenic derivative of the major peach allergen Pru p 3 and to characterize its biochemical and immunologic properties. Methods: A Pru p 3 folding variant generated by means of reduction and alkylation was investigated for structural integrity and stability to gastrointestinal enzymes. IgE reactivity and allergenic potency were determined by means of immunoblotting, ELISA, and in vitro mediator release assay with sera from patients with peach allergy. T-cell immunogenicity was investigated by using human allergen-specific T cells and CBA/J mice immunized with either native Pru p 3 (nPru p 3) or reduced and alkylated (R/A) Pru p 3. Pru p 3 processing by endolysosomal fractions of dendritic cells and antigenicity was examined in mice. Results: Unfolding of Pru p 3 reduced its high resistance to gastrointestinal proteolysis and almost completely abrogated its IgE reactivity and allergenic potency. However, R/A Pru p 3 was capable of stimulating human and murine T cells. Endolysosomal degradation of R/A Pru p 3 was accelerated in comparison with nPru p 3, but similar peptides were generated. IgG and IgE antibodies raised against nPru p 3 showed almost no cross-reactivity with R/A Pru p 3. Moreover, the antigenicity of R/A Pru p 3 was strongly reduced. Conclusion: Unfolded Pru p 3 showed reduced allergenicity and antigenicity and preserved T-cell immunogenicity. The hypoallergenic variant of Pru p 3 could be a promising vaccine candidate for specific immunotherapy of peach allergy.

Original languageEnglish
Pages (from-to)1022-1030.e7
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number5
DOIs
Publication statusPublished - 2011 Nov
Externally publishedYes

Keywords

  • Pru p 3
  • allergen-specific immunotherapy
  • antigenicity
  • folding variant
  • hypoallergen
  • immunogenicity
  • nonspecific lipid transfer protein

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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