Reconstitution of H-2 class I expression by gene transfection decreases susceptibility to natural killer cells of an EL4 class I loss variant.
Several reports have suggested that an inverse correlation exists between major histocompatibility complex class I expression and the susceptibility to natural killer (NK)-mediated lysis. For example, the increased class I expression induced by interferon-gamma was always accompanied by an increased resistance to NK lysis. Likewise, class I loss variants were often more NK susceptible than their normal counterparts. To investigate whether the inverse correlation between class I expression and NK susceptibility was fortuitous or whether the class I molecules were directly responsible for this effect we resorted to gene transfection studies. From the murine thymoma line EL4 and H-2Db- and Kb-negative variant S3 was selected. This variant was highly susceptible to NK lysis. S3 was found to have a defect in beta 2-microglobulin gene expression. Therefore, restoration of Db and Kb expression could be achieved by transfection with the beta 2-microglobulin gene. This resulted in a strong decrease in susceptibility to NK lysis to the level of the H-2+ parental EL4. Transfection with class II genes had no effect. Blocking of the class I molecules on the H-2+ cells with anti-H-2b F(ab')2 fragments increased the susceptibility to NK cells to the level of the H-2- variant S3. These data demonstrate that the class I molecules on the targets are directly responsible for regulation of NK susceptibility but the mechanism is not clear. Possibly the class I molecules interfere with the unknown NK target structures.
Sturmhöfel
K
K
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
Hämmerling
G J
GJ
D000818:Animals; D000937:Antigen-Antibody Reactions; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D011994:Recombinant Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics
D006183:H-2 Antigens; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D007371:Interferon-gamma