Common tetrasaccharide epitope NeuAc alpha 2-->3Gal beta 1-->3(Neu-Ac alpha 2-->6)GalNAc, presented by different carrier glycosylceramides or O-linked peptides, is recognized by different antibodies and ligands having distinct specificities.
A novel globo-series disialoganglioside, disialosyl galactosyl globoside (Structure 1 below), defined by new monoclonal antibody (mAb) RM2, was isolated and characterized as having terminal structure identical to that of ganglio-series ganglioside GD1 alpha (Structure 2) and a common mucin-type epitope (Structure 3) widely distributed in glycoproteins such as glycophorin A. While these three structures share a common nonreducing tetrasaccharide terminus, mAb RM2 showed strong specific reactivity only with Structure 1, not with Structures 2 or 3. Another mAb, QSH2, reacted strongly with Structure 3 but did not cross-react with Structures 1 or 2. Conformational molecular models based on minimum energy hard sphere exoanomeric calculations suggest that Structure 1 presents a unique surface topology distinct from that of Structures 2 or 3. Our findings suggest the novel concept that reactivity of a common carbohydrate epitope with different antibodies or ligands is highly dependent on the type of carrier glycosylceramide or carrier O-linked peptide. [formula: see text]
Saito
S
S
Biomembrane Institute, Seattle, Washington 98119.
Levery
S B
SB
Salyan
M E
ME
Goldberg
R I
RI
Hakomori
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002518:Ceramides / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005732:Gangliosides / Q000737:chemistry* / Q000276:immunology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002518:Ceramides; D000939:Epitopes; D005732:Gangliosides; D010455:Peptides; C086047:disialosyl galactosyl globoside