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. Human NK effector cells, enriched by nylon wool passage, were incubated with monoclonal antibodies (MoAb) to MHC-I followed by cross-linking with secondary rabbit anti mouse Ig or streptavidin. Cross linking of MHC-I molecules on NK cells resulted in a clear inhibition of the NK activity against the target cells K562, Molt-4 and U937. The inhibitory effect was selective for MHC-I and was not seen with MoAb to MHC-II or CD56 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 intact antibody. The best inhibition of NK activity was obtained using biotin-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 on NK cells can be involved in the regulation of NK cytotoxicity, perhaps by transmitting inhibitory signals into the NK cell.
Petersson
M G
MG
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Grönberg
A
A
Kiessling
R
R
Ferm
M T
MT
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I