Antibodies reacting with neighboring gangliosides

MOYANO AL; FUNES SC; NORES GA

Buenos Aires

Simposio; GlycoAR 2014; 2014

The concept of "density dependent" binding of antibodies was proposed in the middle 80´s to explain the behavior of amelanoma-specific monoclonal antibody that recognized GM3, a ubiquitous ganglioside. More recently, antibodies recognizing two different gangliosides have been described in Guillain-Barré syndrome (GBS) patients. Although the nature of the recognized antigen is not identified, it has been proposed that the antibodies would bind a complex formed by different gangliosides. Immunization of rabbits with bovine brain gangliosides induced an experimental neuropathy, with clinical signs resembling GBS. All the immunized animals developed IgG-immunoreactivity to GM1 ganglioside. In a few (4 out of 27) animals, an additional anti-ganglioside antibody populationshowing an unusual binding behavior was detected. Enzymelinkedimmunosorbent assay and TLC-immunostaining analyses showed that binding of these unusual antibodies required the presence of two co-localized gangliosides. Maximal interaction was observed to a mixture of GM1 and GD1b, but the antibodies also showed "density-dependent" binding to GD1b, indicating that two molecules of GD1b sufficiently close together were also recognized. The antibodies were purified by affinity chromatography, and displayed the ability to target antigens in biological membranes(rat synaptosomes).