THE C-TERMINUS OF IFN-GAMMA IS SUFFICIENT FOR INTRACELLULAR FUNCTION

We have previously shown that murine interferon gamma (IFN gamma) and its C-terminal peptide, muIFN gamma(95-133), bind to a region on the c ytoplasmic domain of the IFN gamma receptor contained in the synthetic peptide, MIR(253-287). This region of the murine receptor bears consi derable homology (approximate to 80%) to its human counterpart. Here w e report that not only do human IFN gamma and the human IFN gamma C-te rminal peptide, huIFN gamma(95-134), bind to the cytoplasmic domain of the human IFN gamma receptor, but also that this interaction is speci es non-specific. MuIFN gamma(95-133) binds to human IFN gamma receptor cytoplasmic peptide HIR(252-291), and huIFN gamma(95-134) binds to MI R(253-287). Furthermore, treatment of murine macrophage cell lines wit h C-terminal peptides of either murine or human IFN gamma results in 1 0-fold upregulation of MHC class II molecule expression and increased resistance to infection with vesicular stomatitis virus (VSV) (10(6) - 10(9)-fold reduction in yield). These data suggest a direct role for the C-terminus of IFN gamma in the initiation of intracellular signall ing processes and may be indicative of a more general mechanism of act ion for extracellular signalling molecules. (C) 1994 Academic Press, I nc.