Structure of a Ganglioside with Cad Blood Group Antigen Activity

Baiba K. Gillard, Dominique Blanchard, Jean Francois Bouhours, Jean Pierre Cartron, J. Albert van Kuik, Johannis P. Kamerling, Johannes F.G. Vliegenthart, Donald M. Marcus

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The Cad antigen is a rare erythrocyte blood group antigen expressed on both sialoglycoprotein and ganglioside structures. It is related both serologically and biochemically to the Sda blood group antigen expressed on over 90% of Caucasian erythrocytes. We reported previously that Cad erythrocytes contain a novel ganglioside that binds Helix pomatia lectin and inhibits human anti-Sda antibody. We have now purified the Cad ganglioside and determined its structure. The ganglioside contained Gk-Gal-GlcNAcGalNAc-NeuAc in a molar ratio of 1.00:1.94:0.95:0.93:1.05,. Its chromatographic mobility was between that of GM1 and GD3. After treatrnent with β-hexosaminidase (human placenta Hex A), the product migrated with 2-3-sialosylparagloboside (IV3NeuAcnLc4OseCer), it no longer bound H. pomatia lectin, and it acquired the ability to bind an antibody to sialosylparagloboside. Treatment of this material with neuraminidase (Vibrio cholerae) yielded a product with the mobility of paragloboside (nLc4OseCer) that bound monoclonal antibody 1B2, which is specific for terminal N-acetyllactosaminyl structures. Treatment of the Cad ganglioside with Arthrobacter ureafaciens neuraminidase yielded a product reactive with monoclonal antibody 2D4, which is specific for terminal GalNAcβ(1-4)Gal structures. These data provide strong evidence that the Cad ganglioside structure is GalNAcβ(1-4)[NeuAcα(2-3)]Galβ(1-4)GlcNAcβ(1-3)Galβ(1- 4)GlcCer. 1H NMR analysis also supports the conclusion that the terminal GalNAc is linked β(1-4) to Gal. High-performance thin-layer chromatographic ganglioside patterns from three blood group Cad individuals showed a direct correlation between the quantity of Cad ganglioside and the strength of Cad antigen expression on the erythrocytes, as measured by hemagglutination. In addition to the major Cad ganglioside, a minor, slower moving component reactive with H. pomatia lectin was detected in all three Cad samples. No H, pomatia reactive bands were detected in gangliosides isolated from Sd(a+) cells, and the red cell component carrying the Sda antigen remains to be identified.

Original languageEnglish (US)
Pages (from-to)4601-4606
Number of pages6
JournalBiochemistry
Volume27
Issue number13
DOIs
StatePublished - Jun 1 1988

ASJC Scopus subject areas

  • Biochemistry

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