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*
Protein Structure Group, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark; and
Biochemical Allergy Research, ALK-Abelló, Hørsholm, Denmark
The symptoms characteristic of allergic hypersensitivity are caused
by the release of mediators, i.e., histamine, from effector cells such
as basophils and mast cells. Allergens with more than one B cell
epitope cross-link IgE Abs bound to high affinity Fc
RI receptors on
mast cell surfaces leading to aggregation and subsequent mediator
release. Thus, allergen-Ab complexes play a crucial role in the cascade
leading to the allergic response. We here report the structure of a 1:1
complex between the major birch pollen allergen Bet v 1 and the Fab
fragment from a murine monoclonal IgG1 Ab, BV16, that has been solved
to 2.9 Å resolution by x-ray diffraction. The mAb is shown to inhibit
the binding of allergic patients’ IgE to Bet v 1, and the allergen-IgG
complex may therefore serve as a model for the study of allergen-IgE
interactions relevant in allergy. The size of the BV16 epitope is 931
Å2 as defined by the Bet v 1 Ab interaction surface.
Molecular interactions predicted to occur in the interface are likewise
in agreement with earlier observations on Ag-Ab complexes. The epitope
is formed by amino acids that are conserved among major allergens from
related species within the Fagales order. In combination
with a surprisingly high inhibitory capacity of BV16 with respect to
allergic patients’ serum IgE binding to Bet v 1, these observations
provide experimental support for the proposal of dominant IgE epitopes
located in the conserved surface areas. This model will facilitate the
development of new and safer vaccines for allergen immunotherapy in the
form of mutated allergens.
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