ENGAGEMENT OF MHC CLASS-I PROTEINS ON NATURAL-KILLER-CELLS INHIBITS THEIR KILLING CAPACITY

We have studied whether engagement of MHC class I (MHC-I) molecules on natural killer (NK) cells can influence the NK killing activity. Huma n NK effector cells, enriched by nylon wool passage, were incubated wi th monoclonal antibodies (MoAb) to MHC-I followed by cross-linking wit h secondary rabbit anti mouse Ig or streptavidin. Cross linking of MHC -I molecules on NK cells resulted in a clear inhibition of the NK acti vity against the target cells K562, Molt-4 and U937. The inhibitory ef fect was selective for MHC-I and was not seen with MoAb to MHC-II or C D56 molecules. The inhibition was not mediated via Fc receptors since F(ab)(2) fragments of the MHC-I MoAb W6/32 were as effective as the in tact antibody. The best inhibition of NK activity was obtained using b iotin-labelled F(ab)(2) fragments of W6/32 and streptavidin as a cross -linker, where up to 70 % reduction in NK cell activity was observed. Antibody dependent cellular cytotoxicity (ADCC) was also inhibited by cross-linking MHC-I molecules on the effector cells. The results show that antibody mediated cross-linking of MHC-I proteins on NK cells can inhibit their killing capacity. This indicates that MHC-I molecules o n NK cells can be involved in the regulation of NK cytotoxicity, perha ps by transmitting inhibitory signals into the NK cell.