Dominant epitopes and allergic cross-reactivity: complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1
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Dominant epitopes and allergic cross-reactivity : complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1. / Mirza, Osman Asghar; Henriksen, A; Ipsen, H; Larsen, J N; Wissenbach, M; Spangfort, M D; Gajhede, M.
In: Journal of Immunology, Vol. 165, No. 1, 01.07.2000, p. 331-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dominant epitopes and allergic cross-reactivity
T2 - complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1
AU - Mirza, Osman Asghar
AU - Henriksen, A
AU - Ipsen, H
AU - Larsen, J N
AU - Wissenbach, M
AU - Spangfort, M D
AU - Gajhede, M
PY - 2000/7/1
Y1 - 2000/7/1
N2 - 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 FcepsilonRI 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 A 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 A2 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.
AB - 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 FcepsilonRI 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 A 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 A2 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.
KW - Allergens
KW - Animals
KW - Antibodies, Monoclonal
KW - Antibody Specificity
KW - Antigens, Plant
KW - Computer Simulation
KW - Cross Reactions
KW - Humans
KW - Immunodominant Epitopes
KW - Immunoglobulin Fab Fragments
KW - Immunoglobulin G
KW - Mice
KW - Models, Molecular
KW - Plant Proteins
KW - Pollen
KW - Rhinitis, Allergic, Seasonal
KW - Rosales
KW - Trees
M3 - Journal article
C2 - 10861069
VL - 165
SP - 331
EP - 338
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -
ID: 44864361