Evidence that specific high-mannose oligosaccharides can directly inhibit antigen-driven T-cell responses.

Uromodulln is an 85 Kd Immunosuppressive glycoprotein originally isolated from human pregnancy urine. It is unique In that most of its biologic activity can be attributed to attached oligosaccharides. Purified immunomodulatory ollgosaccharides from uromodulin have been structurally characterized using ‘H-NMR spectroscopy and shown to be Man�7GlcNAc2(M6, M7). Based on these observations, we isolated high-mannose N-type oiigosaccharides and glycopeptides from ovalbumin, soybean agglutinin, and yeast mannan and show that these high-mannose compounds directly inhibit in vitro antigen-driven T-cell proliferation from mlllimolar to nanomolar concentrations. The most active compound was a core mannose ollgosaccharide derived from yeast mannan, M9(y), which acts to block early events required for normal antigen processing/presentation. These data emphasize the potential functional role of carbohydrate structure in regulating the human Immune response.