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

Uromodulin 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 oligosaccharides from uromodulin have been structurally characterized using 1H-NMR spectroscopy and shown to be Man6-7GlcNAc2(M6,M7). Based on these observations, we isolated high-mannose N-type oligosaccharides 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 millimolar to nanomolar concentrations. The most active compound was a core mannose oligosaccharide 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.