High and low affinity carbohydrate ligands revealed for murine SIGN-R1 by carbohydrate array and cell binding approaches, and differing specificities for SIGN-R3 and langerin

被引:123
作者
Galustian, C
Park, CG
Chai, WG
Kiso, M
Bruening, SA
Kang, YS
Steinman, RM
Feizi, T
机构
[1] Univ London Imperial Coll Sci Technol & Med, Glycosci Lab, Harrow HA1 3UJ, Middx, England
[2] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA
[3] Rockefeller Univ, Chris Browne Ctr Immunol & Immune Dis, New York, NY 10021 USA
[4] Gifu Univ, Dept Appl Bioorgan Chem, Gifu 50111, Japan
关键词
carbohydrate-binding-receptors; carbohydrate ligands; dextran-binding; innate immunity; lectin-type receptors;
D O I
10.1093/intimm/dxh089
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The number of receptors of the 'C-type' lectin family is greater than previously thought with a considerable proportion on cells (dendritic cells and macrophages) critical for innate immunity. Establishing that they bind carbohydrates, unravelling and comparing details of their ligands is crucial for understanding the molecular basis of the cell-cell and cell-pathogen interactions that they mediate. Here we use carbohydrate arrays as a new approach to discovering the ligands of three recently described C-type lectin-type receptors on antigen-presenting cells: murine SIGN-R1, SIGN-R3 and langerin. The arrays encompass an extensive panel including polysaccharides, glycoproteins, oligosaccharides and monosaccharides. These are probed with soluble forms of the receptors (IgG-Fc chimeras). The dominant specificities found for SIGN-R1 and SIGN-R3 are mannose- and fucose-related, as expressed on high mannose type N-glycans and Lewis(a/b)/Lewis(x/y)-type sequences, respectively, with subtle differences between the receptors. The dominant specificity for langerin is unique so far: a Lewis(x)-related sequence with sulfate at position 6 of the terminal galactose. The polysaccharide dextran, known from classical studies to elicit a T-independent response, and whose cellular uptake has been shown recently to be mediated by membrane-associated SIGN-R1, gave no binding signals with the soluble form of the protein. We highlight here the additional need for cell-based assays for detecting biologically relevant low affinity ligands, for we show with SIGN-R1-transfected cells that dextran is such a low affinity ligand for SIGN-R1 that binding is detectable only with the cell membrane-associated receptor. But there is a close relationship between dextran recognition and mannose/fucose recognition, with dextran- and mannose-conjugates co-localizing in intracellular compartments.
引用
收藏
页码:853 / 866
页数:14
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