The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin-1.,Angewandte Chemie International Edition

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The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin-1.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2019-11-07 , DOI: 10.1002/anie.201911875
Yoshiyuki Manabe _{1,

2} , Roberta Marchetti ₃ , Yohei Takakura ₁ , Masahiro Nagasaki ₁ , Wataru Nihei ₁ , Tomoyuki Takebe ₁ , Katsunori Tanaka _{1,

4} , Kazuya Kabayama _{1,

2} , Fabrizio Chiodo ₅ , Shinya Hanashima ₁ , Yoshihiro Kamada ₆ , Eiji Miyoshi ₆ , Hari Prasad Dulal ₇ , Yoshiki Yamaguchi ₈ , Yoshiyuki Adachi ₉ , Naohito Ohno ₉ , Hiroshi Tanaka ₁₀ , Alba Silipo ₃ , Koichi Fukase _{1,

2} , Antonio Molinaro _{1,

3}

Affiliation

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.

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.

中文翻译：

IgG抗体上的核心岩藻糖是Dectin-1的内源性配体。

核心岩藻糖是N-聚糖的主要修饰形式，与免疫调节有关，例如减弱抗体药物依赖抗体的细胞介导的细胞毒性，并通过促进PD-1表达来抑制抗肿瘤反应在T细胞上尽管核心岩藻糖调节许多生物过程，但尚未在哺乳动物中鉴定出核心岩藻糖识别分子。本文中，我们报道Dectin-1（一种已知的抗β-葡聚糖凝集素）识别IgG抗体上的核心岩藻糖。生物物理实验的组合进一步表明，Dectin-1可识别糖基化位点N-端天冬酰胺附近的芳族氨基酸以及核心岩藻糖。因此，

更新日期：2019-11-07

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