Binding of nuclear factors to the IFN-gamma consensus sequence of the human HLA-DR alpha gene: effects of IFN-gamma on tumor cell lines.

The binding of nuclear proteins from human tumor cells to synthetic double stranded oligonucleotides mimicking upstream regions of the HLA-DR alpha gene was studied. As the HLA-DR alpha gene is inducible by interferon(IFN)-gamma, nuclear extracts were also purified from IFN-gamma treated cells. Our data indicate that a) nuclear binding proteins (named IFN-gamma-B3 and Z-B1/B2) are detectable, specific for the IFN-gamma and Z boxes of the human HLA-DR alpha gene; b) both IFN-gamma-B3 and Z-B1/B2 are present in HLA-D negative cell lines and c) the content of IFN-gamma-B3 and Z-B1/B2 is not modulated by IFN-gamma treatment. These data suggest that the presence in the nuclear compartment of these factors, presumably necessary for the correct regulation of the HLA-DR alpha gene, is not sufficient to explain its differential constitutive and induced expression in a variety of in vitro cultured cell lines of different lineage.