IgE-binding epitopes of enolases, a class of highly conserved fungal allergens

J Allergy Clin Immunol. 2000 Nov;106(5):887-95. doi: 10.1067/mai.2000.110799.

Abstract

Background: Cladosporium herbarum and Alternaria alternata are two of the most prominent fungal species inducing type I allergy. Previously, we have demonstrated that enolase (Cla h 6) is the second most important allergen of C herbarum in terms of frequency of sensitization.

Objective: IgE-reactive B-cell epitopes of C herbarum enolase were analyzed, and cross-reactivity between fungal enolases was investigated.

Methods: Cla h 6 glutathione-S-transferase fusion peptides were constructed by means of PCR cloning. A alternata enolase (Alt a 5) was isolated by screening a complementary (c)DNA expression library with a C herbarum enolase DNA probe.

Results: Mapping of Cla h 6 IgE-binding epitopes identified a peptide with a length of 69 amino acids (peptide 9), which bound IgE from 8 of 8 patients. Analysis of the conformation of peptide 9 revealed that it does not form a compact structure but rather spans the whole length of the protein, with side chains exposed to solvent at 3 locations. Peptide 9 in the context of Escherichia coli glutathione-S-transferase not only binds IgE but also competitively inhibits IgE binding to Alt a 5. This result indicates that the epitope or epitopes on peptide 9 constitute a major cross-reacting epitope or epitopes on the enolases from C herbarum and A alternata in the case of the one patient tested.

Conclusions: We demonstrated that the glycolytic enzyme enolase is an allergen not only in C herbarum but also in A alternata. Additionally, enolase was shown to exhibit high cross-reactivity to other fungal enolases. On the basis of the results presented here, we propose the use of recombinant Cla h 6 or maybe even peptide 9 of Cla h 6 for diagnosis and possibly therapy of mold allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / chemistry
  • Allergens / genetics
  • Allergens / immunology*
  • Alternaria / enzymology*
  • Alternaria / genetics
  • Alternaria / immunology
  • Antibodies, Fungal / immunology*
  • Antigens, Fungal / chemistry
  • Antigens, Fungal / genetics
  • Antigens, Fungal / immunology*
  • Cladosporium / enzymology*
  • Cladosporium / genetics
  • Cladosporium / immunology
  • Cloning, Molecular
  • Epitope Mapping / methods
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology*
  • Humans
  • Immunoglobulin E / immunology*
  • Mutagenesis, Site-Directed
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / immunology
  • Phosphopyruvate Hydratase / chemistry
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / immunology*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Sequence Analysis, DNA / methods

Substances

  • Allergens
  • Antibodies, Fungal
  • Antigens, Fungal
  • Epitopes, B-Lymphocyte
  • Peptides
  • Recombinant Fusion Proteins
  • Immunoglobulin E
  • Phosphopyruvate Hydratase