The core fucose on an IgG antibody is an endogenous ligand of Dectin-1

Yoshiyuki Manabe, Roberta Marchetti, Yohei Takakura, Masahiro Nagasaki, Wataru Nihei, Tomoyuki Takebe, Katsunori Tanaka, Kazuya Kabayama, Fabrizio Chiodo, Shinya Hanashima, Yoshihiro Kamada, Eiji Miyoshi, Hari Prasad Dulal, Yoshiki Yamaguchi, Yoshiyuki Adachi, Naohito Ohno, Hiroshi Tanaka, Alba Silipo, Koichi Fukase, Antonio Molinaro

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The core fucose, a major modification of N-glycans, is implicated in immune regulation, such as the attenuation of the antibody-dependent cell-mediated cytotoxicity of antibody drugs and the inhibition of anti-tumor responses via the promotion of PD-1 expression on T cells. Although the core fucose regulates many biological processes, no core fucose recognition molecule has been identified in mammals. Herein, we report that Dectin-1, a known anti-β-glucan lectin, recognizes the core fucose on IgG antibodies. A combination of biophysical experiments further suggested that Dectin-1 recognizes aromatic amino acids adjacent to the N-terminal asparagine at the glycosylation site as well as the core fucose. Thus, Dectin-1 appears to be the first lectin-like molecule involved in the heterovalent and specific recognition of characteristic N-glycans on antibodies.

Original languageEnglish
Pages (from-to)18697-18702
Number of pages6
JournalAngewandte Chemie International Edition in English
Volume58
Issue number51
DOIs
Publication statusPublished - 16 Dec 2019

Cite this

Manabe, Y., Marchetti, R., Takakura, Y., Nagasaki, M., Nihei, W., Takebe, T., ... Molinaro, A. (2019). The core fucose on an IgG antibody is an endogenous ligand of Dectin-1. Angewandte Chemie International Edition in English, 58(51), 18697-18702. https://doi.org/10.1002/anie.201911875