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

Osman Asghar Mirza; A Henriksen; H Ipsen; J N Larsen; M Wissenbach; M D Spangfort; M Gajhede

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

Osman Asghar Mirza, A Henriksen, H Ipsen, J N Larsen, M Wissenbach, M D Spangfort, M Gajhede

170 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Immunology
Volume	165
Issue number	1
Pages (from-to)	331-8
Number of pages	8
ISSN	0022-1767
Publication status	Published - 1 Jul 2000

Keywords

Allergens
Animals
Antibodies, Monoclonal
Antibody Specificity
Antigens, Plant
Computer Simulation
Cross Reactions
Humans
Immunodominant Epitopes
Immunoglobulin Fab Fragments
Immunoglobulin G
Mice
Models, Molecular
Plant Proteins
Pollen
Rhinitis, Allergic, Seasonal
Rosales
Trees

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

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 et al.

In: Journal of Immunology, Vol. 165, No. 1, 01.07.2000, p. 331-8.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{723c4c601b6a4ca4b312ddfec318cfc9,

title = "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",

abstract = "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.",

keywords = "Allergens, Animals, Antibodies, Monoclonal, Antibody Specificity, Antigens, Plant, Computer Simulation, Cross Reactions, Humans, Immunodominant Epitopes, Immunoglobulin Fab Fragments, Immunoglobulin G, Mice, Models, Molecular, Plant Proteins, Pollen, Rhinitis, Allergic, Seasonal, Rosales, Trees",

author = "Mirza, {Osman Asghar} and A Henriksen and H Ipsen and Larsen, {J N} and M Wissenbach and Spangfort, {M D} and M Gajhede",

year = "2000",

month = jul,

day = "1",

language = "English",

volume = "165",

pages = "331--8",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "1",

}

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

SN - 0022-1767

VL - 165

SP - 331

EP - 338

JO - Journal of Immunology

JF - Journal of Immunology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

Fingerprint

Cite this