Structure of a patient-derived antibody in complex with allergen reveals simultaneous conventional and superantigen-like recognition.

Proceedings of the National Academy of Sciences of the United States of America
Alkistis N MitropoulouBrian J Sutton

Abstract

Antibodies classically bind antigens via their complementarity-determining regions, but an alternative mode of interaction involving V-domain framework regions has been observed for some B cell "superantigens." We report the crystal structure of an antibody employing both modes of interaction simultaneously and binding two antigen molecules. This human antibody from an allergic individual binds to the grass pollen allergen Phl p 7. Not only are two allergen molecules bound to each antibody fragment (Fab) but also each allergen molecule is bound by two Fabs: One epitope is recognized classically, the other in a superantigen-like manner. A single allergen molecule thus cross-links two identical Fabs, contrary to the one-antibody-one-epitope dogma, which dictates that a dimeric allergen at least is required for this to occur. Allergens trigger immediate hypersensitivity reactions by cross-linking receptor-bound IgE molecules on effector cells. We found that monomeric Phl p 7 induced degranulation of basophils sensitized solely with this monoclonal antibody expressed as an IgE, demonstrating that the dual specificity has functional consequences. The monomeric state of Phl p 7 and two structurally related allergens was confirmed by ...Continue Reading

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Citations

Mar 1, 2019·Current Allergy and Asthma Reports·Geoffrey A MuellerLars C Pedersen
Sep 27, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jill GlesnerAnna Pomés
Oct 5, 2019·Acta Crystallographica. Section F, Structural Biology Communications·Clement Angkawidjaja, Takashi Torashima
Jul 29, 2020·Protein Engineering, Design & Selection : PEDS·Monica L Fernández-QuinteroKlaus R Liedl
Sep 4, 2020·Biomedicines·Marie-Paule Lefranc, Gérard Lefranc
Feb 2, 2019·Frontiers in Immunology·Julia Eckl-DornaRudolf Valenta
Sep 24, 2019·Antibodies·Brian J SuttonSophia N Karagiannis
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May 9, 2019·Nucleic Acids Research·Fabio Dall'Antonia, Walter Keller
Sep 29, 2020·Frontiers in Immunology·Anna PomésMaksymilian Chruszcz
Jan 30, 2021·Frontiers in Molecular Biosciences·Florian HoferKlaus R Liedl

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Methods Mentioned

BETA
NMR
X-ray
surface plasmon resonance
PISA
light scattering
biopsy
transfection
chip
Assay

Software Mentioned

MolProbity
Coot
PISA
OMNISEC
Biacore T200
XDS
CCP4 Suite
Astra
PHENIX

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