Reconstitution of H‐2 class I expression by gene transfection decreases susceptibility to natural killer cells of an EL4 class I loss variant

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Abstract
Several reports have suggested that an inverse correlation exists between major histocompatibility complex class I expression and the susceptibility to natural killer (NK)‐mediatedlysis. For example, the increased class I expression induced by interferon‐γ 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 an 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 β2‐microglobulin gene expression. Therefore, restoration of Db and Kb expression could be achieved by transfection with the β2‐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.