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Evidence That Specific High‐Mannose Oligosaccharides Can Directly Inhibit Antigen‐Driven T‐Cell Responses
Author(s) -
Muchmore Andrew V.,
Sathyamoorthy Neeraja,
Decker Jean,
Sherblom Anne P.
Publication year - 1990
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.48.5.457
Subject(s) - mannose , mannan , oligosaccharide , biology , biochemistry , antigen , glycoprotein , ovalbumin , mannose receptor , immune system , in vitro , immunology , polysaccharide , macrophage
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 1 H‐NMR spectroscopy and shown to be Man 6–7 GlcNAc 2 (M6,117). 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.