Allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of IgE F(ab')2 epitopes.

Autor: Hirano T; Department of Hematology, Juntendo University Nerima Hospital, Nerima-ku, Tokyo, Japan. thirano@juntendo.ac.jp., Koyanagi A; Laboratory of Cell Biology, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan., Ago H; Advanced Photon Technology Division, RIKEN SPring-8 Center, Sayo, Hyogo, Japan., Yamamoto M; Advanced Photon Technology Division, RIKEN SPring-8 Center, Sayo, Hyogo, Japan., Kitaura J; Atopy Research Center, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.; Department of Science of Allergy and Inflammation, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan., Kasai M; Atopy Research Center, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan., Okumura K; Atopy Research Center, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Aug 23; Vol. 7 (1), pp. 1042. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1038/s42003-024-06633-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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