Anti-ganglioside antibodies bind with enhanced affinity to gangliosides containing very long chain fatty acids.
Gangliosides function in both physiological and pathological molecular recognition. Although much research has focused on the role of ganglioside glycans in recognition, fewer studies have addressed the role of the ceramide moiety. Ceramides of major brain gangliosides are composed predominantly of monounsaturated 18-carbon and 20-carbon long chain bases with a saturated 18-carbon fatty acid amide. In contrast, gangliosides of X-linked adrenoleukodystrophy patients are characterized by abnormal very long chain fatty acids that are proposed to be associated with autoimmune inflammation. In the current study we synthesized and characterized derivatives of the major brain ganglioside GD1a bearing defined very long chain fatty acid amides (C24:0, C24:1, and C26:0). When tested in a solid phase binding assay in the presence of auxiliary membrane lipids, GD1a species with long chain fatty acids were up to 8-fold more potent than normal brain GD1a in binding four different anti-GD1a monoclonal antibodies. These data support the hypothesis that gangliosides bearing very long chain fatty acids are differentially displayed on membranes, which may lead to altered antigenicity.
Tagawa
Yumi
Y
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Laroy
Wouter
W
Nimrichter
Leonardo
L
Fromholt
Susan E
SE
Moser
Ann B
AB
Moser
Hugo W
HW
Schnaar
Ronald L
RL
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000915:Antibody Affinity; D002417:Cattle; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000378:metabolism*; D005732:Gangliosides / Q000276:immunology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000906:Antibodies; D005227:Fatty Acids; D005732:Gangliosides; C021298:ganglioside, GD1a