M161Ag is a potent cytokine inducer with complement activating function (review)

We discovered a membrane-associated novel gene product expressed on some malignant human cells/cell lines undergoing apoptosis. This protein, named M161Ag, activated human complement and efficiently induced the pro-inflammatory cytokines IL-1 Beta , TNF-alpha and IL-6, and also IL-10 and IL-12 in human peripheral blood monocytes. M161Ag was a 43 kDa palmitoylated protein containing five amino acids encoded by TGA codons. These TGA codons were found to be translated into Trp, consistent with expression in prokaryotes including mitochondria and mycoplasma. The amino-terminal lipid was characteristic of prokaryote proteins participating in membrane anchoring. The M161Ag genomic clone contained a Pribnow box at the -35 and -10 promoter portions and the Shine-Dalgarno ribosomal binding site approximately 10 bp upstream of the translational start codon. The Mycoplasma fermentans origin of this protein was then confirmed by genomic Southern analysis; cells only infected with M. fermentans were positive for M161Ag. Thus, latent infection with M. fermentans allows tumor cells to produce M161Ag leading to activation of the host immune system. Here, we summarize bacterial proteins resembling M161Ag which may be candidates for therapeutic use if they exert immuno-regulatory functions.