Dominant epitopes and allergic cross-reactivity: Complex formation betweena Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1

The symptoms characteristic of allergic hypersensitivity are caused by the release of mediators, i.e., histamine, from effector cells such as basophil s and mast cells. Allergens with more than one B cell epitope cross-link Ig E Abs bound to high affinity Fc epsilon RI receptors on mast cell surfaces leading to aggregation and subsequent mediator release. Thus, allergen-Ab c omplexes play a crucial role in the cascade leading to the allergic respons e. We here report the structure of a 1:1 complex between the major birch po llen allergen Bet v 1 and the Fab fragment from a murine monoclonal IgG1 Ab , BV16, that has been solved to 2.9 Angstrom resolution by x-ray diffractio n, 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 s tudy of allergen-IgE interactions relevant in allergy. The size of the BV16 epitope is 931 Angstrom(2) as defined by the Bet v 1 Ab interaction surfac e. Molecular interactions predicted to occur in the interface are likewise in agreement with earlier observations on Ag-Ab complexes. The epitope is f ormed by amino acids that are conserved among major allergens from related species within the Fagales order. In combination with a surprisingly high i nhibitory capacity of BV16 with respect to allergic patients' serum IgE bin ding to Bet v 1, these observations provide experimental support for the pr oposal of dominant IgE epitopes located in the conserved surface areas, Thi s model will facilitate the development of new and safer vaccines for aller gen immunotherapy in the form of mutated allergens.