Allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of IgE F(ab')2 epitopes.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
12
06
2023
accepted:
24
07
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
Immunoglobulin E (IgE) plays pivotal roles in allergic diseases through interaction with a high-affinity receptor (FcεRI). We established that Fab fragments of anti-IgE antibodies (HMK-12 Fab) rapidly dissociate preformed IgE-FcεRI complexes in a temperature-dependent manner and inhibit IgE-mediated anaphylactic reactions, even after allergen challenge. X-ray crystallographic studies revealed that HMK-12 Fab interacts with each of two equivalent epitopes on the Cε2 homodimer domain involved in IgE F(ab')2. Consequently, HMK-12 Fab-mediated targeting of Cε2 reduced the binding affinity of Fc domains and resulted in rapid removal of IgE from the receptor complex. This unexpected finding of allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of two epitope sites on the Cε2 homodimer domain of IgE F(ab')2 may have implications for the development of novel therapies for allergic disease.
Identifiants
pubmed: 39179708
doi: 10.1038/s42003-024-06633-4
pii: 10.1038/s42003-024-06633-4
doi:
Substances chimiques
Immunoglobulin E
37341-29-0
Receptors, IgE
0
Immunoglobulin Fab Fragments
0
Epitopes
0
anti-IgE antibodies
0
Antibodies, Anti-Idiotypic
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1042Subventions
Organisme : Japan Society for the Promotion of Science London (JSPS London)
ID : 21K08447
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21am0101070
Informations de copyright
© 2024. The Author(s).
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