The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin-1.

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

Journal: Angewandte Chemie (International ed. in English) 2020;58(51):18697-18702

PMID: 31625659

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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.

Address: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.; Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.; Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, 80126, Napoli, Italy.; Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.; Amsterdam UMC, Vrije Universiteit Amsterdam, Dept. of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.; Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan.; Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.; Laboratory of Pharmaceutical Physical Chemistry, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan.; Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.; Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H-101, Ookayama, Meguro, Tokyo, 152-8552, Japan.

DOI: 10.1002/anie.201911875

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MeSH Terms: Fucose, Humans, Immunoglobulin G, Lectins, C-Type, Ligands