Genetic control of neutralizing antibody response to mouse interferon in rats

Various strains of rats were immunized weekly with mouse interferon (IFN containing both IFN-alpha and IFN-beta). Their sera were examined for the ability to neutralize the antiviral activity of IFN in a microtiter assay. DA and ACI (RT-1a), BN (RT-1n), and WF (RT-1w) strains of rats produced anti-IFN antibodies after a minimum of four inoculations. In contrast, neither Lewis (RT-1l) nor Buffalo (RT-1b) strains of rats produced any detectable anti-IFN antibodies even after 12 weekly inoculations of IFN. This lack of responsiveness could not be overcome by immunization in the presence of Freund's complete adjuvant. The genetic basis of this difference in antibody response was examined using F1 and back-cross generations of rats. Both (ACI X LEW) F1 and (LEW X ACI) F1 rats produced titers of anti-IFN antibody intermediate to the parental strains. No maternal or paternal effects were observed. Results from the back-cross generation of F1 rats to the parental strains suggested that although the major histocompatibility complex may be a factor in control of this response, other genes are also involved.