Human monoclonal antibodies to myelin-associated glycoprotein. Comparison of specificity and use for immunocytochemical localisation of the antigen.

Recent reports demonstrate that a population of patients with gammopathy and demyelinating neuropathy have monoclonal antibodies to myelin-associated glycoprotein. Using the immunoblotting technique we compared the species specificity: human monoclonal antibodies to myelin-associated glycoprotein reacted with human, monkey, calf, dog, rabbit and guinea pig myelin, but not with rat or mouse. On the immunoblot myelin-associated glycoprotein consistently stained as a diffuse band with an apparent molecular weight ranging from 90-100 X 10(3) dalton. Experiments showed that when human CNS myelin had been incubated at 37 degrees C before gel electrophoresis, there was a general shift of staining towards the lower end of the molecular weight range. This low molecular weight myelin-associated glycoprotein, when released from the membrane, contains the antigenic determinant. Peptide mapping by limited proteolysis reveals that the antigenic determinants for 4 different monoclonal antibodies appear to lie very close together in the molecule. The distribution of the antigen was studied in nervous tissue with the unlabelled peroxidase-antiperoxidase method. The results obtained are in close agreement with the localization reported with polyclonal antisera to myelin-associated glycoprotein.