Characterization of a novel IRF-1-deficient mutant cell line.
The transcriptional activation of the major histocompatibility complex (MHC) class I genes by both type I (alpha/beta) and II (gamma) interferons (IFNs) has been extensively studied, and it has been shown that the upregulation of several DNA-binding proteins is critical for this process. In our laboratory, we introduced the mouse H-2Kb gene into the AKR mouse leukaemia cell line K36.16 to effect the generation of tumor-specific immunity. Individual clones were selected and studied. Whereas the MHC class I genes in most of the clones obtained could be stimulated by interferons, one of the clones obtained, clone Kb-S27, failed to be induced, or was at best poorly induced by IFN-alpha/beta and -gamma. Both the exogenous H-2Kb and the endogenous H-2Dk genes behaved in the same manner and were not stimulated by IFNs. The lack of response to IFNs by clone Kb-S27 also resulted in its resistance to the antiproliferative effects of IFNs. This lack of IFN-induction by clone Kb-S27 was not simply due to a change in its surface interferon receptors. Gel-retardation assay and northern blot analysis both demonstrated the lack of induction of the IRF-1 DNA-binding factor in clone Kb-S27. In addition, northern blot analysis showed that the IRF-2 gene expression in clone Kb-S27 was upregulated when compared with the other IFN-inducible clones.
Lim
S P
SP
Laboratory of Molecular Immunology, National University of Singapore.
Hui
K M
KM
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002999:Clone Cells; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D008806:Mice, Inbred AKR; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D014158:Transcription, Genetic; D014170:Transformation, Genetic; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007372:Interferons; D010750:Phosphoproteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D012097:Repressor Proteins; D014157:Transcription Factors; D000096743:Interferon gamma Receptor; C032876:H-2Kb protein, mouse; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse