Mucin-type O-glycosylation in helminth parasites from major taxonomic groups: evidence for widespread distribution of the Tn antigen (GalNAc-Ser/Thr) and identification of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase activity

J Parasitol. 2003 Aug;89(4):709-14. doi: 10.1645/GE-2970.

Abstract

This article focuses on the initiation pathway of mucin-type O-glycosylation in helminth parasites. The presence of the GalNAc-O-Ser/Thr structure, also known as Tn antigen, a truncated determinant related to aberrant glycosylation in mammal cells, and the activity of the UDP-GalNAc:polypeptide N-acetyl-galactosaminyltransferase (ppGaNTase), the enzyme responsible for its synthesis, were studied in species from major taxonomic groups. Tn reactivity was determined in extracts from Taenia hydatigena, Mesocestoides corti, Fasciola hepatica, Nippostrongylus brasiliensis, and Toxocara canis using the monoclonal antibody 83D4. The Tn determinant was revealed in all preparations, and multiple patterns of Tn-bearing glycoproteins were observed by immunoblotting. Additionally, the first evidence that helminth parasites express ppGaNTase activity was obtained. This enzyme was studied in extracts from Echinococcus granulosus, F. hepatica, and T. canis by measuring the incorporation of UDP-(3H)GalNAc to both deglycosylated ovine syalomucin (dOSM) and synthetic peptide sequences derived from tandem repeats of human mucins. Whereas significant levels of ppGaNTase activity were detected in all the extracts when dOSM was used as a multisite acceptor, it was only observed in F. hepatica and E. granulosus extracts when mucin-derived peptides were used, suggesting that T. canis ppGaNTase enzyme(s) may represent a member of the gene family with a more restricted specificity for worm O-glycosylation motifs. The widespread expression of Tn antigen, capable of evoking both humoral and cellular immunity, strongly suggests that simple mucin-type O-glycosylation does not constitute an aberrant phenomenon in helminth parasites.

MeSH terms

  • Animals
  • Antigens, Tumor-Associated, Carbohydrate / chemistry
  • Antigens, Tumor-Associated, Carbohydrate / metabolism*
  • Blotting, Western
  • Cattle
  • Dogs
  • Echinococcus / enzymology
  • Echinococcus / immunology
  • Echinococcus / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Fasciola hepatica / enzymology
  • Fasciola hepatica / immunology
  • Fasciola hepatica / metabolism
  • Glycopeptides / metabolism
  • Glycoproteins / analysis
  • Glycosylation
  • Helminths / enzymology
  • Helminths / immunology
  • Helminths / metabolism*
  • Humans
  • Mesocestoides / enzymology
  • Mesocestoides / immunology
  • Mesocestoides / metabolism
  • Mice
  • N-Acetylgalactosaminyltransferases / metabolism*
  • Nippostrongylus / enzymology
  • Nippostrongylus / immunology
  • Nippostrongylus / metabolism
  • Rats
  • Rats, Wistar
  • Taenia / enzymology
  • Taenia / immunology
  • Taenia / metabolism
  • Toxocara canis / enzymology
  • Toxocara canis / immunology
  • Toxocara canis / metabolism

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Glycopeptides
  • Glycoproteins
  • Tn antigen
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase