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.
Department of Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
B L
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Li
X X
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Zhao
X Y
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Liu
H S
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Kim
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Raska
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JR
Ortaldo
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B
Schwartz
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Pestka
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010957:Plasmids; D011994:Recombinant Proteins; D015183:Restriction Mapping; D013329:Structure-Activity Relationship
D007370:Interferon Type I; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins