Carcinoma autoantigens T and Tn and their cleavage products interact with Gal/GalNAc-specific receptors on rat Kupffer cells and hepatocytes.
We studied interactions of isolated Thomsen-Friedenreich (T)- and Tn-specific glycoproteins with the Gal/GalNAc-specific receptors on rat Kupffer cells and compared them to those with rat hepatocytes. Immunoreactive T and Tn are specific pancarcinoma epitopes. Electron microscopy of gold-labelled T and Tn antigens revealed their specific binding to Kupffer cells, followed by their uptake via the coated pit/vesicle pathway of receptor-mediated endocytosis. Preincubation of Kupffer cells with GalNAc and GalNAc-BSA, but not GlcNAc or GlcNAc-BSA specifically inhibited binding of the T and Tn glycoproteins. Desialylated, isologous erythrocytes (T RBC) are known to bind to the Gal/GalNAc receptors of rat Kupffer cells and hepatocytes. This attachment was specifically inhibited by T and Tn in a concentration-dependent manner: 50% T RBC-Kupffer cell contacts were inhibited at 8.5.10(-6) mM T and 8.5.10(-5) mM Tn antigen concentrations, respectively. The corresponding figures for hepatocytes were 6.10(-6) mM T and 1.2.10(-6) mM Tn antigen. Amino-terminal cleavage products of the T glycoprotein, possessing clusters terminating in non-reducing Gal/GalNAc, inhibited T RBC binding to Kupffer cells and hepatocytes usually at 10(-2) to 10(-5) mM concentrations, whereas GalNAc, galactose and galactose glycosides inhibited at millimolar concentrations. Galactose-unrelated carbohydrates were inactive at concentrations greater than or equal to 50 mM.
Schlepper-Schäfer
J
J
Faculty of Biology, University of Konstanz, F.R.G.
Springer
G F
GF
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate; D001324:Autoantigens / Q000276:immunology; D002448:Cell Adhesion; D004187:Disaccharides / Q000276:immunology*; D004705:Endocytosis; D004912:Erythrocytes / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D001324:Autoantigens; D004187:Disaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C040286:Tn antigen; C039707:galactose receptor; C037045:galactose-N-acetylgalactosamine receptor; C016467:Thomsen-Friedenreich antigen