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

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‐2D^b‐ and K^b‐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 D^b and K^b 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‐2^b 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.