Susceptibility to natural killer cell-mediated cytolysis is independent of the level of target cell class I HLA expression.
To test the hypothesis that susceptibility to NK cell-mediated cytolysis varies inversely with the levels of target cell class I HLA expression, NK-susceptible K562 and MOLT-4 target cells have been transfected via electroporation with cloned human class I HLA-A2 and HLA-B7 genes. Stably transfected cells expressing varying levels of cell-surface class I HLA have been selected by fluorescent activated cell sorting and tested for susceptibility to NK-mediated cytolysis by freshly isolated peripheral blood NK cells from nine normal volunteers as well as by cloned human NK effectors and tumor cells from a patient with an NK cell lymphoproliferative disorder. Expression of class I HLA did not alter the susceptibility of K562 or MOLT-4 target cells to NK-mediated cytolysis by any of the effectors tested. In addition, the class I HLA-expressing transfectant cells were identical to mock transfected cells in their ability to compete for lysis in cold target inhibition assays. Treatment of both mock-transfected and class I HLA-transfected K562 cells with IFN-gamma resulted in decreased susceptibility to NK-mediated cytolysis which was independent of the total level of class I HLA expression. These results demonstrate that the level of target cell class I HLA expression is not sufficient to determine susceptibility or resistance to NK-mediated cytolysis of the classical NK targets K562 and MOLT-4.
Leiden
J M
JM
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48105.
Karpinski
B A
BA
Gottschalk
L
L
Kornbluth
J
J
D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000276:immunology; D015458:Leukemia, T-Cell / Q000235:genetics / Q000276:immunology; D014162:Transfection
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma