Resistance to NK cell-mediated cytotoxicity (in K-562 cells) does not correlate with class I MHC antigen levels.
Natural Killer (NK) cells probably function as an early line of defense against virus-infected cells and tumor cells. In all cases, the killing by NK cell-mediated cytotoxicity (NK-CMC) is not MHC-restricted and the factors which determine the sensitivity to NK-CMC have not yet been identified. A positive correlation between resistance to NK-CMC and the level of class I MHC antigen (MHC I) expression on target cells has been reported in many studies, and in some cases a functional linkage between the two has been claimed. Several other studies have shown that there is no such correlation. By employing several experimental systems, we demonstrate here a lack of correlation between the level of MHC I and the sensitivity of K-562 cells to NK-CMC. Transfer of MHC I to MHC I-negative cells via vesicles had no effect on their resistance to NK-CMC. In addition, a decrease in resistance to NK-CMC and increase of MHC I levels was observed following target-cell membrane modulation by both application of cholesterol and hydrostatic pressure. Finally, no correlation between sensitivity to NK-CMC and MHC I expression was found in three sublines of K-562 cells. Since NK-CMC is a multistage process, it is concluded that components other than class I MHC antigens have a more prominent role in modulating the sensitivity of target cells to NK-CMC.
Reiter
Z
Z
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Reiter
Y
Y
Fishelson
Z
Z
Shinitzky
M
M
Kessler
A
A
Loyter
A
A
Nussbaum
O
O
Rubinstein
M
M
D016923:Cell Death; D002461:Cell Line, Transformed / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002784:Cholesterol / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D006874:Hydrostatic Pressure; D007113:Immunity, Innate; D007371:Interferon-gamma; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008561:Membrane Fusion; D008567:Membranes, Artificial; D013539:Simian virus 40 / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D008567:Membranes, Artificial; D007371:Interferon-gamma; D002784:Cholesterol