Antibodies to the Carboxyl Terminus of Mouse Interferon-γ Neutralize its Immunoregulatory and Antiviral Activities

Antibodies to a synthetic carboxy-terminal peptide (Cys-Ser-Leu-Arg-Lys-Arg-Lys-Arg-Ser-Arg-Abu) (gamma-C-TP) of mouse interferon-gamma (MuIFN-gamma) were produced in rabbits. They neutralized the antiviral activity of MuIFN-gamma but not that of MuIFN-alpha/beta or human (Hu) IFN-alpha/beta or -gamma. They also inhibited the IFN-dependent enhancement of natural cytotoxic cells (NCC) and the in vivo plaque-forming cell (PFC) response to sheep red blood cells (SRBC). Thus, our results indicate that polyclonal antibodies specific for the nine carboxy-terminal amino acids of MuIFN-gamma can specifically inhibit the antiviral and immunoregulatory activities of this IFN in vitro. In addition, our findings indicate that endogenous production of MuIFN-gamma in vivo plays a role in development of the full antibody response to SRBC surface antigens.