Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: Importance for allergenic activity

Sabine Flicker, Peter Steinberger, Tanja Ball, Maria Theresa Krauth, Petra Verdino, Peter Valent, Steve Almo, Rudolf Valenta

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background: The major timothy grass pollen allergen Phl p 1 is one of the most potent and frequently recognized environmental allergens. Objective: We sought to study at a molecular and structural level the IgE recognition of Phl p 1 and its relation to allergenic activity. Methods: Monoclonal human IgE antibody fragments specific for Phl p 1 and group 1 allergens from various grasses were isolated from a combinatorial library made of lymphocytes from patients with grass pollen allergy. Recombinant Phl p 1 fragments and the 3-dimensional structure of Phl p 1 were used to localize the major binding site for the IgE antibodies. A rPhl p 1 fragment containing this binding site was expressed in Escherichia coli, purified, and tested for IgE reactivity and allergenic activity with sera and basophils from patients with grass pollen allergy. Results: Monoclonal antibodies, as well as polyclonal serum IgE, from patients with grass pollen allergy defined a C-terminal fragment of Phl p 1 that represents a sterically oriented portion on the Phl p 1 structure. This Phl p 1 portion bound most of the allergen-specific IgE antibodies and contained the majority of the allergenic activity of Phl p 1. Conclusion: IgE recognition of spatially clustered epitopes on allergens might be a general factor determining their allergenic activity. Clinical implications: Geographic distribution of IgE epitopes on an allergen might influence its allergenic activity and hence explain discrepancies between diagnostic test results based on IgE serology and provocation testing. It might also form a basis for the development of low allergenic vaccines.

Original languageEnglish (US)
Pages (from-to)1336-1343
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume117
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • 3-dimensional structure
  • Grass pollen allergy
  • Phl p 1
  • allergen
  • epitope
  • monoclonal human IgE antibodies
  • recombinant allergen fragment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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