Allosteric Inhibition of IgE-FcεRI Interactions by Simultaneous Targeting of IgE F(ab')2 Epitopes

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Aug 23

PMID 39179708

Authors

Takao Hirano

Akemi Koyanagi

Hideo Ago

Masaki Yamamoto

Jiro Kitaura

Masataka Kasai

Ko Okumura

Affiliations

Soon will be listed here.

Abstract

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.

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