Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: Importance for allergenic activity - 20/08/11
Vienna, Austria, New York, NY, and La Jolla, Calif
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.
Le texte complet de cet article est disponible en PDF.Key words : Grass pollen allergy, allergen, Phl p 1, 3-dimensional structure, recombinant allergen fragment, epitope, monoclonal human IgE antibodies
Abbreviations used : CDR, Fab, FR, GST
Plan
Supported by grants T165-B09, F01809, F01815, and Schroedinger grant J2122 to TB of the Austrian Science Fund and a research grant from Biomay, Vienna, Austria. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interset. |
Vol 117 - N° 6
P. 1336-1343 - juin 2006 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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