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-Interferon Structure and Natural Killer Cell Stimulatory Activity¹

Departments of Molecular Genetics and Microbiology [B.-L. L., X-X. Z., X-Y. L., B. S., S. P.] and Pathology [H. S. K., K. R.], University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland 21701 [J. R. O.]

Expression vectors for human -interferon (Hu-IFN-) J1, a site-specific mutant [Ser¹¹⁶]Hu-IFN-J1, and Hu-IFN-J/C or Hu-IFN-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 -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- 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.

¹ This research was supported in part by grants AI-25914 and CA-46465 to Sidney Pestka and grants AI-25914 and CA-21196 to Karel Raska, Jr., from the NIH.

² Present address: Shanghai Institute of Biochemistry, Academia Sinica, 320 Yue-Yang Road, Shanghai, China.

³ Present address: Institute of Virology, China National Centre for Preventive Medicine, Beijing, China.

⁴ To whom requests for reprints should be addressed, at Department of Molecular Genetics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635.

Received 2/14/90. Revised 5/ 8/90.

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