Specific inhibition of human natural killer cell-mediated cytotoxicity by sialic acid and sialo-oligosaccharides

We have tried to identify carbohydrate structures involved in recognition and/or lysis of K562 target cells by human natural killer (NK) cells. Inhibition studies were performed with mono-, di-and trisaccharides, and with glycopeptides and glycoproteins of known carbohydrate composition. When tested with various monosaccharides, lysis of K562 cells was inhibited only by N-acetylneuraminic acid (NeuAc). Di-and trisaccharides and glycopeptides containing NeuAc or N-glycolylneuraminic acid (NeuGc) all inhibited NK cell-mediated lysis. Among the non-sialylated carbohydrates tested, only Galβ(1→3)GalNAcol was effective. The inhibitory capacity of sialylated compounds appeared to be dependent on the linkage type of the sialic acid residue; carbohydrates containing α(2→6)-linked sialic acids were more potent inhibitors than their α(2→3) isomers. Also the sugar to which the sialic acid residue was attached was of importance, NeuAcα(2→6)GalNAcol being more effective than NeuAcα(2→6)Galßl→R (where R= glucose or oligo-saccharide-peptide). Sialylated compounds and free sialic acid had minor or no effects on cell-mediated cytotoxicity by allo-sensitized cytotoxic T lymphocytes. The conjugation of target cells and NK effector cells was not inhibited by carbohydrates that effectively blocked the cytolytic response. These results may indicate that cell-surface carbohydrates containing α(2→6)-linked sialic acid are crucial structures in a post-binding event in NK-cell-mediated lysis.