Similar localization of conformational IgE epitopes on the house dust mite allergens Der p 5 and Der p 21 despite limited IgE cross-reactivity

Allergy. 2018 Aug;73(8):1653-1661. doi: 10.1111/all.13398. Epub 2018 Feb 21.

Abstract

Background: Due to high IgE recognition frequency and high allergenic activity, Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens. The objective of this study was to characterize the immunodominant IgE epitopes of Der p 5 and Der p 21 responsible for their high allergenic activity.

Methods: A panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence were synthesized to search for sequential IgE epitopes by direct testing for allergic patients' IgE reactivity. Peptide-specific antibodies raised in rabbits were used in inhibition studies for localizing conformational IgE epitopes which were visualized on the surfaces of the allergen structures by molecular modelling. IgE cross-reactivity between the allergens was investigated by IgE inhibition studies.

Results: Immunodominant IgE epitopes defined by allergic patients' IgE on Der p 5 and Der p 21 were primarily of the conformational, discontinuous type including N- and C-terminal portions of the protein. They could be located on each allergen on one area with similar localization, but despite similar structure of the allergens, no relevant IgE cross-reactivity could be detected.

Conclusion: Our study shows that Der p 5 and Der p 21 contain a major conformational IgE epitope-containing area located on similar portions of their structure, but they lack relevant IgE cross-reactivity. These data are important for the development of modern allergy vaccines based on defined molecules for allergen-specific immunotherapy of HDM allergy.

Keywords: IgE epitope mapping; allergen; allergy; cross-reactivity; house dust mite allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Antigens, Dermatophagoides / chemistry*
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins / chemical synthesis
  • Arthropod Proteins / chemistry*
  • Arthropod Proteins / immunology*
  • Cross Reactions / immunology*
  • Drug Discovery
  • Epitope Mapping
  • Epitopes / chemistry*
  • Epitopes / immunology
  • Humans
  • Immunization
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology*
  • Immunoglobulin G / immunology
  • Models, Molecular
  • Molecular Conformation
  • Protein Conformation, alpha-Helical
  • Protein Folding
  • Pyroglyphidae / immunology*
  • Rabbits
  • Vaccines, Synthetic

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Dermatophagoides pteronyssinus antigen p 5
  • Epitopes
  • Immunoglobulin G
  • Vaccines, Synthetic
  • Immunoglobulin E