Role of target cell glycoproteins in sensitivity to natural killer cell lysis.
Natural killer cells select targets for lysis based on target cell glycoproteins. Compared to controls, K-562 cells treated with kifunensine, an inhibitor of Golgi mannosidase I, accumulate more high mannose-type asparagine-linked oligosaccharide, Man9GlcNAc2, and bind more concanavalin A, an oligomannosyl binding lectin. In addition, natural killer cell lysis of kifunensine-treated cells increases 34% over that of controls. Increased sensitivity to lysis occurs after treatment with other N-glycan processing inhibitors that promote accumulation of high mannose-type glycosides (deoxymannojirimycin and swainsonine). In addition, kifunensine-treated cells form more effector:target conjugates. Monoclonal antibodies to the adhesion molecule LFA-1 and its ligand ICAM-1 reduce lysis of control targets but are less effective in blocking lysis of kifunensine-treated cells. K-562 cells bind anti-ICAM-1 but not anti-LFA-1, and this binding does not change after kifunensine treatment. These data demonstrate conclusively a role for asparagine-linked oligosaccharides in the human natural killer cell:target interaction. The presence of high mannose-type glycans on K-562 cells correlates with increased binding of effectors and a greater susceptibility to lysis. These results support the idea that target cell N-glycosides influence the NK-target interaction mediated by adhesion molecules such as ICAM-1.
Ahrens
P B
PB
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226.
D017485:1-Deoxynojirimycin / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules / Q000276:immunology; D003208:Concanavalin A / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000276:immunology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D007694:Killer Cells, Natural / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017026:Swainsonine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D000470:Alkaloids; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D003208:Concanavalin A; D006023:Glycoproteins; D006026:Glycoside Hydrolases; D007212:Indolizines; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1; D008361:Mannosidases; D009844:Oligosaccharides; D017026:Swainsonine; C065629:kifunensine; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase; C037806:castanospermine; D054836:Indolizidines