Glycobiology Advance Access published online on September 13, 2007
Glycobiology, doi:10.1093/glycob/cwm095
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Sulfatide binding properties of murine and human anti-ganglioside antibodies
1 Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, Scotland G12 8TA
2 Institute of Physiological Chemistry, University of Bonn, Nussallee 11, D-53115 Bonn, Germany
3 Laboratory of Carbohydrate Chemistry, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow
4 CERMAV-CNRS, BP53, F-38041, GRENOBLE, cedex 9, France
5 Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Correspondence: Dr Kate Townson, Division of Clinical Neurosciences, Room B333, Glasgow Biomedical Research Centre, University of Glasgow, Scotland G12 8TA, Tel: +44 141 330 8388; Fax: +44 141 330 4297; email: k.townson{at}clinmed.gla.ac.uk
Received on May 10, 2007; accepted on September 3, 2007
Anti-ganglioside antibodies form an important component of the innate and adaptive B cell repertoire, where they provide anti-microbial activity through binding encapsulated bacterial glycans. In an aberrant role, they target peripheral nerve gangliosides to induce autoimmune nerve injury. An important characteristic of anti-ganglioside antibodies is their ability to selectively recognise highly defined glycan structures. Since sialylayted and sulfated glycans often share lectin recognition patterns, we here explored the possibility that certain anti-ganglioside antibodies might also bind 3-O-sulfo-ß-D-galactosylceramide (sulfatide), an abundant constituent of plasma and peripheral nerve myelin, that could thereby influence any immunoregulatory or autoimmune properties. Out of 25 anti-ganglioside antibodies screened in solid phase assays, 20 also bound sulfatide (10–5 to 10–6M range) in addition to their favoured 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-ß-D-galactose were unique in having this property amongst a wide range of sulphated glycans screened, including 4- and 6-O-sulfo-ß-D-galactose analogues. Anti-ganglioside antibody binding to 3-O-sulfo-ß-D-galactose was highly dependent upon the spatial presentation of the ligand, being completely inhibited by conjugation to protein or polyacrylamide 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 anti-ganglioside antibodies that may provide functional insights into, and consequences for this component of the innate immune repertoire.
Key words: Antibody / sulfatide / ganglioside / neuropathy