Conformational IgE epitopes of peanut allergens Ara h 2 and Ara h 6

X. Chen, S. S. Negi, S. Liao, V. Gao, Werner Braun, S. C. Dreskin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Cross-linking of IgE antibody by specific epitopes on the surface of mast cells is a prerequisite for triggering symptoms of peanut allergy. IgE epitopes are frequently categorized as linear or conformational epitopes. Although linear IgE-binding epitopes of peanut allergens have been defined, little is known about conformational IgE-binding epitopes. Objective: To identify clinically relevant conformational IgE epitopes of the two most important peanut allergens, Ara h 2 and Ara h 6, using phage peptide library. Methods: A phage 12mer peptide library was screened with allergen-specific IgE from 4 peanut-allergic patients. Binding of the mimotopes to IgE from a total of 29 peanut-allergic subjects was measured by ELISA. The mimotope sequences were mapped on the surface areas of Ara h 2 and Ara h 6 using EpiSearch. Results: Forty-one individual mimotopes were identified that specifically bind anti- Ara h 2/Ara h 6 IgE as well as rabbit anti-Ara h 2 and anti-Ara h 6 IgG. Sequence alignment showed that none of the mimotope sequences match a linear segment of the Ara h 2 or Ara h 6 sequences. EpiSearch analysis showed that all the mimotopes mapped to surface patches of Ara h 2 and Ara h 6. Eight of the mimotopes were recognized by more than 90% of the patients, suggesting immunodominance. Each patient had distinct IgE recognition patterns but the recognition frequency was not correlated to the concentration of peanut specific IgE or to clinical history. Conclusions: The mimotopes identified in this study represent conformational epitopes. Identification of similar surface patches on Ara h 2 and Ara h 6 further underscores the similarities between these two potent allergens.

Original languageEnglish (US)
Pages (from-to)1120-1128
Number of pages9
JournalClinical and Experimental Allergy
Volume46
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

Immunoglobulin E
Epitopes
Allergens
Peptide Library
Bacteriophages
Peanut Hypersensitivity
Arachis hypogaea Ara h 2 allergen
Sequence Alignment
Mast Cells
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Rabbits
Arachis
Antibodies

Keywords

  • allergens
  • Ara h 2
  • Ara h 6
  • EpiSearch
  • epitopes
  • IgE
  • mimotopes
  • peanut
  • phage display

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Conformational IgE epitopes of peanut allergens Ara h 2 and Ara h 6. / Chen, X.; Negi, S. S.; Liao, S.; Gao, V.; Braun, Werner; Dreskin, S. C.

In: Clinical and Experimental Allergy, Vol. 46, No. 8, 01.08.2016, p. 1120-1128.

Research output: Contribution to journalArticle

Chen, X. ; Negi, S. S. ; Liao, S. ; Gao, V. ; Braun, Werner ; Dreskin, S. C. / Conformational IgE epitopes of peanut allergens Ara h 2 and Ara h 6. In: Clinical and Experimental Allergy. 2016 ; Vol. 46, No. 8. pp. 1120-1128.
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N2 - Background: Cross-linking of IgE antibody by specific epitopes on the surface of mast cells is a prerequisite for triggering symptoms of peanut allergy. IgE epitopes are frequently categorized as linear or conformational epitopes. Although linear IgE-binding epitopes of peanut allergens have been defined, little is known about conformational IgE-binding epitopes. Objective: To identify clinically relevant conformational IgE epitopes of the two most important peanut allergens, Ara h 2 and Ara h 6, using phage peptide library. Methods: A phage 12mer peptide library was screened with allergen-specific IgE from 4 peanut-allergic patients. Binding of the mimotopes to IgE from a total of 29 peanut-allergic subjects was measured by ELISA. The mimotope sequences were mapped on the surface areas of Ara h 2 and Ara h 6 using EpiSearch. Results: Forty-one individual mimotopes were identified that specifically bind anti- Ara h 2/Ara h 6 IgE as well as rabbit anti-Ara h 2 and anti-Ara h 6 IgG. Sequence alignment showed that none of the mimotope sequences match a linear segment of the Ara h 2 or Ara h 6 sequences. EpiSearch analysis showed that all the mimotopes mapped to surface patches of Ara h 2 and Ara h 6. Eight of the mimotopes were recognized by more than 90% of the patients, suggesting immunodominance. Each patient had distinct IgE recognition patterns but the recognition frequency was not correlated to the concentration of peanut specific IgE or to clinical history. Conclusions: The mimotopes identified in this study represent conformational epitopes. Identification of similar surface patches on Ara h 2 and Ara h 6 further underscores the similarities between these two potent allergens.

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