title: An IgG monoclonal antibody against Dictyostelium discoideum glycoproteins specifically recognizes Fucalpha1,6GlcNAcbeta in the core of N-linked glycans. Localized expression of core-fucosylated glycoconjugates in human tissues.
abstract: Core fucosylation of N-linked oligosaccharides (GlcNAcbeta1, 4(Fucalpha1,6)GlcNAcbeta1-Asn) is a common modification in animal glycans, but little is known about the distribution of core-fucosylated glycoproteins in mammalian tissues. Two monoclonal antibodies, CAB2 and CAB4, previously raised against carbohydrate epitopes of Dictyostelium discoideum glycoproteins (Crandall, I. E. and Newell, P. C. (1989) Development 107, 87-94), specifically recognize fucose residues in alpha1,6-linkage to the asparagine-bound GlcNAc of N-linked oligosaccharides. These IgG3 antibodies do not cross-react with glycoproteins containing alpha-fucoses in other linkages commonly seen in N- or O-linked sugar chains. CAB4 recognizes core alpha1,6 fucose regardless of terminal sugars, branching pattern, sialic acid linkage, or polylactosamine substitution. This contrasts to lentil and pea lectins that recognize a similar epitope in only a subset of these structures. Additional GlcNAc residues found in the core of N-glycans from dominant Chinese hamster ovary cell mutants LEC14 and LEC18 progressively decrease binding. These antibodies show that many proteins in human tissues are core-fucosylated, but their expression is localized to skin keratinocytes, vascular and visceral smooth muscle cells, epithelia, and some extracellular matrix-like material surrounding subpopulations of lymphocytes. The availability of these antibodies now allows for an extended investigation of core fucose epitope expression in development and malignancy and in genetically manipulated mice.
authors.affiliation: Burnham Institute, La Jolla, California 92037, USA.
authors.forename: G
authors.initials: G
authors.lastname: Srikrishna
authors.forename: N M
authors.initials: NM
authors.lastname: Varki
authors.forename: P C
authors.initials: PC
authors.lastname: Newell
authors.forename: A
authors.initials: A
authors.lastname: Varki
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015153:Blotting, Western; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006224:Cricetinae; D004023:Dictyostelium / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D004921:Erythropoietin / Q000378:metabolism; D005643:Fucose / Q000276:immunology*; D006001:Glycoconjugates / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007983:Lewis Blood Group Antigens / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D006001:Glycoconjugates; D006023:Glycoproteins; D007074:Immunoglobulin G; D007983:Lewis Blood Group Antigens; D011134:Polysaccharides; D004921:Erythropoietin; D005643:Fucose; D010741:Phospholipases A