Inhibition of activity of human NK and K cells by simple sugars: discrimination between binding and postbinding events.

A variety of sugars were tested for their ability to inhibit the lytic activity of highly purified populations of human natural killer (NK) cells (large granular lymphocytes [LGL] ). Studies were also performed to determine whether inhibitory sugars were active at the level of recognition and binding to target cells (as determined by conjugate formation) or at a postbinding lytic stage. Mannose-6-PO4 and galactose-6-PO4 demonstrated strong and consistent inhibition of NK cytolysis at 50 mM concentration, while nonphosphorylated analogs were at most minimally effective. The inhibitory phosphorylated sugars did not block conjugate formation, indicating that the sugars affected some postbinding event rather than recognition of target cells by NK cells. The inhibition of NK activity by some sugars was not paralleled by inhibition of antibody-dependent cellular cytotoxicity (ADCC) activity by LGL. This suggests some divergence in the lytic mechanisms for NK and ADCC.