Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor.

  • U Gubler
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • A O Chua
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • D S Schoenhaut
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • C M Dwyer
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • W McComas
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • R Motyka
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • N Nabavi
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • A G Wolitzky
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • P M Quinn
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
  • P C Familletti
    Department of Molecular Genetics, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110.

抄録

<jats:p>Cytotoxic lymphocyte maturation factor (CLMF) is a disulfide-bonded heterodimeric lymphokine that (i) acts as a growth factor for activated T cells independent of interleukin 2 and (ii) synergizes with suboptimal concentrations of interleukin 2 to induce lymphokine-activated killer cells. We now report the cloning and expression of both human CLMF subunit cDNAs from a lymphoblastoid B-cell line, NC-37. The two subunits represent two distinct and unrelated gene products whose mRNAs are coordinately induced upon activation of NC-37 cells. Coexpression of the two subunit cDNAs in COS cells is necessary for the secretion of biologically active CLMF; COS cells transfected with either subunit cDNA alone do not secrete bioactive CLMF. Recombinant CLMF expressed in mammalian cells displays biologic activities essentially identical to natural CLMF, and its activities can be neutralized by monoclonal antibodies prepared against natural CLMF. Since this heterodimeric protein displays the properties of an interleukin, we propose that CLMF be given the designation interleukin 12.</jats:p>

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