title: The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose.
abstract: We examined the carbohydrate-binding potential of the C-type lectin-like receptor Dectin-2 (Clecf4n). The carbohydrate-recognition domain (CRD) of Dectin-2 exhibited cation-dependent mannose/fucose-like lectin activity, with an IC(50) for mannose of approximately 20 mM compared to an IC(50) of 1.5 mM for the macrophage mannose receptor when assayed by similar methodology. The extracellular domain of Dectin-2 exhibited binding to live Candida albicans and the Saccharomyces-derived particle zymosan. This binding was completely abrogated by cation chelation and was competed by yeast mannans. We compared the lectin activity of Dectin-2 with that of two other C-type lectin receptors (mannose receptor and SIGNR1) known to bind fungal mannans. Both mannose receptor and SIGNR1 were able to bind bacterial capsular polysaccharides derived from Streptococcus pneumoniae, but interestingly they exhibited distinct binding profiles. The Dectin-2 CRD exhibited only weak interactions to some of these capsular polysaccharides, indicative of different structural or affinity requirements for binding, when compared with the other two lectins. Glycan array analysis of the carbohydrate recognition by Dectin-2 indicated specific recognition of high-mannose structures (Man(9)GlcNAc(2)). The differences in the specificity of these three mannose-specific lectins indicate that mannose recognition is mediated by distinct receptors, with unique specificity, that are expressed by discrete subpopulations of cells, and this further highlights the complex nature of carbohydrate recognition by immune cells.
authors.affiliation: Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, UK.
authors.forename: Eamon P
authors.initials: EP
authors.lastname: McGreal
authors.forename: Marcela
authors.initials: M
authors.lastname: Rosas
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Susanne
authors.initials: S
authors.lastname: Zamze
authors.forename: Simon Y C
authors.initials: SY
authors.lastname: Wong
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Luisa
authors.initials: L
authors.lastname: Martinez-Pomares
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
mesh_terms: D001667:Binding, Competitive; D002176:Candida albicans / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D015054:Zymosan / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011994:Recombinant Proteins; C445340:dectin-2, mouse; D015054:Zymosan; D008358:Mannose