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

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Abstract
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.

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