NK-LYSIN, A NOVEL EFFECTOR PEPTIDE OF CYTOTOXIC T-CELLS AND NK-CELLS - STRUCTURE AND CDNA CLONING OF THE PORCINE FORM, INDUCTION BY INTERLEUKIN-2, ANTIBACTERIAL AND ANTITUMOR-ACTIVITY

A 78 residue antimicrobial, basic peptide, NK-lysin, with three intrac hain disulfide bonds was purified from pig small intestine and charact erized. A corresponding clone was isolated from a porcine bone marrow cDNA library. The 780 bp DNA sequence had a reading frame of 129 amino acids which corresponded to NK-lysin. The clone was used to show that stimulation with human interleukin-2 induced synthesis of NK-lysin-sp ecific mRNA in a lymphocyte fraction enriched for T and NK cells. Lowe r levels of mRNA were detected in tissues known to contain T and NR ce lls, such as small intestine, spleen and colon. Interleukin-2 also ind uced both proliferation of the lymphocyte fraction and cytolytic funct ion in these cells. Immunostaining showed that NK-lysin was present in cells positive for CD8, CD2 and CD4. NK-lysin showed high antibacteri al activity against Escherichia coli and Bacillus megaterium and moder ate activity against Acinetobacter calcoaceticus and Streptococcus pyo genes. The peptide showed a marked lytic activity against an NK-sensit ive mouse tumour cell line, YAC-1, but it did not lyse red blood cells . The amino acid sequence of NK-lysin exhibits 33% identity with a put ative human preproprotein, NKG5, of unknown function but derived from a cDNA done of activated NK cells. We suggest that NK-lysin is a new e ffector molecule of cytotoxic T and NK cells.