Variability in the structural requirements for binding of human monoclonal anti-myelin-associated glycoprotein immunoglobulin M antibodies and HNK-1 to sphingoglycolipid antigens.
A high proportion of patients with neuropathy have immunoglobulin M (IgM) paraproteins that react with carbohydrate determinants on the myelin-associated glycoprotein (MAG) and two sphingoglycolipids, 3-sulfoglucuronyl paragloboside (SGPG) and 3-sulfoglucuronyl lactosaminyl paragloboside. In order to characterize the fine specificities of these human antibodies further, the binding of 10 anti-MAG paraproteins to several chemically modified derivatives of SGPG was compared with the binding to intact SGPG by both TLC-overlay and enzyme-linked immunosorbent assay. The following derivatives were tested: the desulfated lipid, glucuronyl paragloboside (GPG); the methyl ester of GPG (MeGPG); the methyl ester of SGPG, 3-sulfomethylglucuronyl paragloboside (SMeGPG); and 3-sulfoglucosyl paragloboside (SGlcPG) produced by reduction of the carboxyl group of the glucuronic acid with sodium borohydride. All 10 IgM paraproteins and the related mouse IgM antibody, HNK-1, reacted most strongly with intact SGPG, but variations in the reactivity with the derivatives revealed striking differences in the structural requirements for binding between the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
A A
AA
Ilyas
D K
DK
Chou
F B
FB
Jungalwala
C
C
Costello
R H
RH
Quarles
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D015153:Blotting, Western; D018959:CD57 Antigens; D002851:Chromatography, High Pressure Liquid; D005915:Globosides / Q000276:immunology; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D008745:Methylation; D015394:Molecular Structure; D009185:Myelin Proteins / Q000276:immunology*; D018992:Myelin-Associated Glycoprotein; D010266:Paraproteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000943:Antigens, Differentiation; D018959:CD57 Antigens; D005915:Globosides; D006028:Glycosphingolipids; D007075:Immunoglobulin M; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D010266:Paraproteins; C051917:sulfate-3-glucuronyl paragloboside; C064938:3-sulfoglucuronyl-lactosaminyl-paragloboside