POST‐TRANSCRIPTIONAL DOWNREGULATION OF MHC CLASS I EXPRESSION IN ONCOGENE‐TRANSFORMED CELLS IS REVERTED BY IFN‐GAMMA AND TNF‐ALPHA

SUMMARY Transformation of murine NIH3T3 fibroblasts with retroviral vectors carrying the mos, myc and the Ha‐ras oncogene, respectively, was associated with a strong reduction of H2 antigen expression in the cell membrane. Analysis of H‐2K and β 2 ‐microglobulin promoter‐driven CAT activity in these oncogenic transformants and normal NIH3T3 fibroblasts revealed unchanged promoter activity, suggesting post‐transcriptional control of MHC class I expression by these oncogenes. Treatment with IFN‐gamma and TNF‐alpha caused 2‐ to 3‐fold enhancement of H‐2K and β 2 ‐microglobulin promoter activity, as well as a normalization (TNF‐alpha treatment) or enhancement (IFN‐gamma treatment) of H2 membrane expression. These data suggest that IFN‐gamma as well as TNF‐alpha can counteract downregulation of H‐2 genes by interference with an oncogene‐induced, post‐transcriptional block as well as by a direct enhancement of H‐2 gene transcription.