Alpha-interferon structure and natural killer cell stimulatory activity

Expression vectors for human alpha-interferon (Hu-IFN-alpha) J1, a site-specific mutant [Ser116]Hu-IFN-alpha J1, and Hu-IFN-alpha J/C or Hu-IFN-alpha C/J hybrids were constructed and expressed in Escherichia coli. These interferons and others were purified by immunoaffinity chromatography with a monoclonal antibody against human alpha-interferon. Their antiviral activity and ability to stimulate natural killer cell activity were determined in comparison to several other human interferons. These results provide some insight into structure-activity relationships for stimulating natural killer cells and confirm our previous conclusions that antiviral activity cannot be used to predict other activities for an individual IFN-alpha species. The observations suggest that the tertiary structure rather than any specific linear sequence of amino acids regulates the ability of the interferons to stimulate natural killer cell activity.