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

Eur J Immunol. 1990 Jan;20(1):171-7. doi: 10.1002/eji.1830200125.


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.

MeSH terms

  • Animals
  • Antigen-Antibody Reactions
  • Cytotoxicity, Immunologic*
  • Gene Expression / drug effects
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology*
  • Immunity, Innate
  • Interferon-gamma / pharmacology
  • Killer Cells, Natural / immunology*
  • Mice
  • Recombinant Proteins
  • Transfection
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / genetics


  • H-2 Antigens
  • Recombinant Proteins
  • beta 2-Microglobulin
  • Interferon-gamma