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) interfe rons (IFNs) has been extensively studied, and it has been shown that t he upregulation of several DNA-binding proteins is critical for this p rocess. In our laboratory, we introduced the mouse H-2K(b) gene into t he AKR mouse leukaemia cell line K36.16 to effect the generation of tu mor-specific immunity. Individual clones were selected and studied. Wh ereas the MHC class I genes in most of the clones obtained could be st imulated by interferons, one of the clones obtained, clone K-b-S27, fa iled to be induced, or was at best poorly induced by IFN-alpha/beta an d -gamma. Both the exogenous N-2K(b) and the endogenous H-2D(k) genes behaved in the same manner and were not stimulated by IFNs. The lack o f response to IFNs by clone K-b-S27 also resulted in its resistance to the antiproliferative effects of IFNs. This lack of IFN-induction by clone K-b-S27 was not simply due to a change in its surface interferon receptors. Gel-retardation assay and northern blot analysis both demo nstrated the lack of induction of the IRF-1 DNA-binding factor in clon e K-b-S27. In addition, northern blot analysis showed that the IRF-2 g ene expression in clone K-b-S27 was upregulated when compared with the other IFN-inducible clones.