title: Sulfatide binding properties of murine and human antiganglioside antibodies.
abstract: Antiganglioside antibodies form an important component of the innate and adaptive B cell repertoire, where they provide antimicrobial activity through binding encapsulated bacterial glycans. In an aberrant role, they target peripheral nerve gangliosides to induce autoimmune nerve injury. An important characteristic of antiganglioside antibodies is their ability to selectively recognize highly defined glycan structures. Since sialylated and sulfated glycans often share lectin recognition patterns, we here explored the possibility that certain antiganglioside antibodies might also bind 3-O-sulfo-beta-D-galactosylceramide (sulfatide), an abundant constituent of plasma and peripheral nerve myelin, that could thereby influence any immunoregulatory or autoimmune properties. Out of 25 antiganglioside antibodies screened in solid phase assays, 20 also bound sulfatide (10(-5) to 10(-6) M range) in addition to their favored ganglioside glycan epitope ( approximately 10(-7) M range). Solution inhibition studies demonstrated competition between ganglioside and sulfatide, indicating close proximity or sharing of the antigen binding variable region domain. Sulfatide and 3-O-sulfo-beta-D-galactose were unique in having this property amongst a wide range of sulfated glycans screened, including 4- and 6-O-sulfo-beta-D-galactose analogues. Antiganglioside antibody binding to 3-O-sulfo-beta-D-galactose was highly dependent upon the spatial presentation of the ligand, being completely inhibited by conjugation to protein or polyacrylamide (PAA) matrices. Binding was also absent when sulfatide was incorporated into plasma membranes, including myelin, under conditions in which antibody binding to ganglioside was retained. These data demonstrate that sulfatide binding is a common property of antiganglioside antibodies that may provide functional insights into, and consequences for this component of the innate immune repertoire.
authors.affiliation: Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, G12 8TA Scotland. k.townson@clinmed.gla.ac.uk
authors.forename: Kate
authors.initials: K
authors.lastname: Townson
authors.forename: Kay N
authors.initials: KN
authors.lastname: Greenshields
authors.forename: Jean
authors.initials: J
authors.lastname: Veitch
authors.forename: Dawn
authors.initials: D
authors.lastname: Nicholl
authors.forename: Matthias
authors.initials: M
authors.lastname: Eckhardt
authors.forename: Oxana
authors.initials: O
authors.lastname: Galanina
authors.forename: Nicolai
authors.initials: N
authors.lastname: Bovin
authors.forename: Eric
authors.initials: E
authors.lastname: Samain
authors.forename: Tatiana
authors.initials: T
authors.lastname: Antoine
authors.forename: David
authors.initials: D
authors.lastname: Bundle
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Chang Chun
authors.initials: CC
authors.lastname: Ling
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D016716:PC12 Cells; D051381:Rats; D013433:Sulfoglycosphingolipids / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005732:Gangliosides; D013433:Sulfoglycosphingolipids