Characterization of a human melanoma-associated ganglioside antigen defined by a monoclonal antibody, 4.2

Abstract

A monoclonal IgM antibody, 4.2, reacting with a surface antigen expressed on most human melanomas (Yeh, M.-I., Hellström, I., Abe, K., Hakomori, S., and Hellström, K. E. (1982) Int. J. Cancer, 29, 269-275) was shown to be directed to a ganglioside with the carbohydrate structure NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 4Glc beta 1 leads to 1Cer. The carbohydrate structure, established by enzymatic degradation and methylation analysis with mass spectrometry, is identical with that of brain GD3 ganglioside, but its ceramide is characterized by a predominance of longer chain fatty acids, in contrast to brain GD3 that has mainly C18:0 fatty acid. The antibody did not react with various other gangliosides, including those having the same terminal sugar sequence (NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal) as GD3, such as GT1a and GQ1b. Its specificity is therefore restricted to the NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 4Glc leads to Cer sequence, including the innermost sugar, Glc residue.