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)