Glycobiology Advance Access originally published online on September 13, 2007
Glycobiology 2007 17(11):1156-1166; doi:10.1093/glycob/cwm095
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Sulfatide binding properties of murine and human antiganglioside antibodies
2 Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, G12 8TA Scotland
3 Institute of Physiological Chemistry, University of Bonn, Nussallee 11, D-53115 Bonn, Germany
4 Laboratory of Carbohydrate Chemistry, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
5 CERMAV-CNRS, BP53, F-38041, GRENOBLE, Cedex 9, France
6 Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
1 To whom correspondence should be addressed: Tel: +44-141-330-8388; Fax: +44-141-330-4297; e-mail: k.townson{at}clinmed.gla.ac.uk
Received on May 10, 2007; revised on August 28, 2007; accepted on September 3, 2007
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-β-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 (
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-β-D-galactose were unique in having this property amongst a wide range of sulfated glycans screened, including 4- and 6-O-sulfo-β-D-galactose analogues. Antiganglioside antibody binding to 3-O-sulfo-β-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.
Key words: antibody / ganglioside / neuropathy / sulfatide