Differential Regulation of the Immune Response to SRBC by Monoclonal Antibodies to Interferon-γ

Three monoclonal antibodies against different epitopes of interferon-γ (IFN-γ) were used to assess its role as a normal immunomodulatory molecule. Two of these antibodies were able to reduce significantly the primary antibody response to sheep erythrocytes in an in vitro culture system. One of these two antibodies has been reported to suppress both the antiviral and macrophage activation factor activities of IFN-γ by binding to its carboxyl terminus. These findings indicate that IFN-γ is an important lymphokine for the maximum expression of the immune response and that it acts via the carboxyl terminus of the molecule. This antibody suppressed the immune response only when added at the initiation of culture, suggesting that the action of IFN-γ is on an early component of the response. The third monoclonal antibody, which binds to the amino end of IFN-γ, did not suppress the in vitro response. However, it was able to block the effects exerted by an immunosuppressive dosage of exogenous IFN-γ on in vitro antibody production. These results indicate that the immunosuppression induced by the addition of IFN-γ to a primary antibody response and the role that it plays in that response are mediated through different sites on the molecule and, therefore, probably by different mechanisms.