Abstract. We investigated whether the L2/HNK-1 carbohydrate epitope, expressed by two unusual glycolipids and several neural adhesion molecules, including L1, neural cell adhesion molecule, J1, and the myelin-associated glycoprotein, is involved in adhesion. Monoclonal L2 antibodies, the L2/HNK-I-reactive, sulfate-3-glucuronyl residue carrying glycolipids (L2 glycolipid) and a tetrasaccharide derived from the L2 glycolipid (L2 tetrasaccharide) were added to microexplant cultures of early postnatal mouse cerebellum, and cell migration and process extension were monitored. On the substrate poly-D-lysine, Fab fragments of L2 antibodies, L2 glycolipid, and L2 tetrasaccharide inhibited outgrowth of astrocytic processes and migration of cell bodies, but only L2 glycolipid and L2 tetrasaccharide reduced neurite outgrowth. On laminin, L2 antibodies, L2 glycolipid, and L2 tetrasaccharide inhibited outgrowth of astrocytic processes.Additionally, L2 glycolipid and L2 tetrasaccharide inhibited cell migration and neurite outgrowth. Several negatively charged glycolipids, lipids, and saccharides were tested for control and found to have no effect on outgrowth patterns, except for sulfatide and heparin, which modified outgrowth patterns in a similar fashion as L2 glycolipid and L2 tetrasaccharide. On astrocytes none of the tested compounds interfered with explant outgrowth. In short-term adhesion assays L2 glycolipid, sulfatide, and heparin inhibited adhesion of neural cells to laminin. L2 glycolipid and sulfatide interfered with neuron to astrocyte and astrocyte to astrocyte adhesion, but not with neuron-neuron adhesion. The most straightforward interpretation of these observations is that the L2/HNK-1 carbohydrate and the sulfated carbohydrates, sulfatide and heparin, act as ligands in cell adhesion.

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To determine whether antibodies to acidic glycolipids of nervous tissue are present in patients with Guillain-Barré syndrome (GBS), sera from patients with GBS and appropriate control subjects were tested by a thin-layer chromatogram overlay technique. Chromatograms on which the whole ganglioside fractions from peripheral nerve and brain had been separated were overlaid with appropriate dilutions of the patients' sera (1:100 or greater), and antibody binding was revealed with a radiolabeled or peroxidase-labeled second antibody. Antibodies to ganglioside antigens were detected in 5 of 26 patients with GBS. IgG antibodies in 1 patient reacted strongly with LM1 (sialosyl paragloboside), the major ganglioside of human peripheral nervous system myelin, and its hexaose analog (sialosyl lactosaminyl paragloboside), a minor ganglioside of human peripheral nervous system myelin. The antibody titer in this patient fell 8-fold over 6 weeks coincident with clinical improvement. IgG from 2 other patients with GBS reacted with GD1b ganglioside, and the antibody titers in these patients also decreased substantially with clinical improvement. IgM antibodies in the sera from 2 other patients reacted with GD1a and GT1b gangliosides, which have a shared terminal carbohydrate sequence. Antibodies to gangliosides were not detected in the sera from 19 patients with other neurological diseases or from 10 normal subjects, and the frequency with which antiganglioside antibodies occurred in the patients with GBS was significantly greater than that in the combined control subjects (p less than 0.01). The results demonstrate relatively high levels of antibodies to gangliosides in some GBS patients.

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Sulfoglucuronyl carbohydrate linked to neolactotetraose reacts with HNK-1 antibody. The HNK-1 carbohydrate epitope is found in two major glycolipids, several glycoproteins and in some proteoglycans of the nervous system. Most of the HNK-1 reactive glycoproteins so far identified are neural cell adhesion molecules and/or are involved in cell-cell interactions. HNK-1 carbohydrate is highly immunogenic. Several HNK-1-like antibodies, including IgM of some patients with plasma cell abnormalities and having peripheral neuropathy, have been described. This article summarizes published work mainly on sulfoglucuronyl glycolipids, SGGLs and covers: structural requirements of the carbohydrate epitope for binding to HNK-1 and human antibodies, expression of the lipids in various neural areas, stage and region specific developmental expression in CNS and PNS, immunocytochemical localization, loss of expression in Purkinje cell abnormality murine mutations, biosynthetic regulation of expression by a single enzyme N-acetylglucosaminyl transferase, identification of receptor-like carbohydrate binding neural proteins (lectins), and perceived role of the carbohydrate in physiological functions. The latter includes role in: pathogenesis of certain peripheral neuropathies, in migration of neural crest cells, as a ligand in cell-cell adhesion/interaction and as a promoter of neurite outgrowth for motor neurons. Multiple expression of HNK-1 carbohydrate in several molecules and in various neural cell types at specific stages of nervous system development has puzzled investigators as to its specific biological function, but this may also suggest its importance in multiple systems during cell differentiation and migration processes.