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Flicker, S; Steinberger, P; Ball, T; Krauth, MT; Verdino, P; Valent, P; Almo, S; Valenta, R.
Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: importance for allergenic activity.
J Allergy Clin Immunol. 2006; 117(6):1336-1343 Doi: 10.1016/j.jaci.2006.02.012
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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.
Find related publications in this database (using NLM MeSH Indexing)
Allergens - genetics Allergens - immunology Allergens - metabolism
Binding Sites - immunology
Cross Reactions -
Epitope Mapping -
Humans -
Immunodominant Epitopes - immunology Immunodominant Epitopes - metabolism
Immunoglobulin E - metabolism
Peptide Fragments - genetics Peptide Fragments - immunology Peptide Fragments - metabolism
Phleum - immunology
Pilot Projects -
Plant Proteins - genetics Plant Proteins - immunology
Pollen - immunology
Rhinitis, Allergic, Seasonal - immunology Rhinitis, Allergic, Seasonal - metabolism

Find related publications in this database (Keywords)
grass pollen allergy
Phl p 1
3-dimensional structure
recombinant allergen fragment
monoclonal human IgE antibodies
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