Murine tumor cells expressing the gene for the human interferon αβ receptor elicit antibodies in syngeneic mice to the active form of the receptor

The cellular receptor for the human α and β interferons (IFN) was expressed, by gene transfer, in a murine hepatoma-derived cell line, BTG 9A. Injected subcutaneously into the syngeneic mouse (C57BL/6), the parental and the transfected cells grew and formed tumors which later regressed. More than half the mice bearing tumors derived from cells expressing the receptor, developed IgG antibodies capable of blocking the activity, on human cells, of human recombinant IFN-αB, -αA, -αD and of natural human IFN-β, but not of recombinant IFN-γ. Cross-reactivity of human IFN-α on murine and bovine cells was unaffected by these antibodies. The binding of human IFN-α to solubilized receptors from human lymphoid cell lines was also blocked and complexes of radiolabeled recombinant IFN-αA or IFN-αB, chemically cross-linked to their human receptor could be immunoprecipitated by the antisera. IFN αβ receptor protein, purified by electrophoresis in sodium dodecylsulfate, was not recognized. We conclude that the antibodies are directed against the forms of the IFN αβ receptor actually expressed on the membrane.