Immunosuppressive activity of tamm-horsfall glycoprotein oligosaccharides: Effect of removal of outer sugars and conjugation with a protein carrier

Fabio Dall'Olio, Mariella Chiricolo, Nadia Malagolini, Claudio Franceschi, Franca Serafini-Cessi

Research output: Contribution to journalArticle

Abstract

Tamm-Horsfall (TH) glycoprotein, the major protein of human urine, is, in vitro, a powerful immunosuppressive agent and the activity resides in its oligosaccharide chains. In this study we investigated structural features required for the inhibitory activity of TH glycoprotein oligosac-charides in the one-way mixed lymphocyte reaction (MLR). We found that both high-mannose and complex-type TH glycopeptides, fractionated from Pronase-digested TH glycoprotein, behaved as inhibitors. Sequential exoglycosidase digestion of complex-type TH glycopeptide results in a slight increase of the inhibitory activity, with a maximum after desialylation and β-galactosidase treatment. These results suggest that the immunosuppressive activity resides in the central portion of TH glycoprotein N-linked oligosaccharides. The conjugation of complex-type TH glycopeptides to a protein carrier, such as bovine serum albumin, greatly enhanced the inhibitory activity. This effect occurred if the TH-glycopeptide conjugate was added to MLR within the first 24 hr. These results indicate that (i) the immunosuppressive activity is strongly dependent on a multivalent interaction between TH oligosaccharides and ligand(s) at the lymphocyte surface; (ii) an early step of cell-cell recognition is the target of the immunosuppressive conjugate; (iii) TH oligosaccharides compete with a carbohydrate recognition system between effector and stimulator cells which contributes to the MLR-induced blastogenesis.

Original languageEnglish
Pages (from-to)303-315
Number of pages13
JournalCellular Immunology
Volume137
Issue number2
DOIs
Publication statusPublished - Oct 15 1991

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ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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