The core fucose on an IgG antibody is an endogenous ligand of Dectin-1
The core fucose is a significant modification of N-glycans and has profound implications in immune regulation. These are 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.
Previous observation on glycan arrays suggested a putative interaction between the mammalian lectin, Dectin-1, and glycan containing fucose residue. A combination of biophysical experiments further indicated that Dectin-1 recognizes aromatic amino acids adjacent to the N-terminal asparagine residue at the glycosylation site as well as core fucose residue. Thus, Dectin-1, known as anti-beta-glucan lectin, appears to be the first lectin-like molecule involved in the hetero-valent and specific recognition of characteristic N-glycans on antibodies. The biological relevance of the recognition of core fucose on IgGs by Dectin-1 remains to be further evaluated.