Adjuvant activity of mycobacterial fractions: adjuvant activity of synthetic N-acetylmuramyl-dipeptide and the related compounds

Abstract

Immunological activity of synthetic [Mycobacterium bovis BCG-like] cell wall peptidoglycan subunits was examined in guinea pigs and mice. The minimal adjuvant-active subunit of cell wall peptidoglycan for the induction of delayed-type hypersensitivity to monoazobenzenearsonate-N-acetyl-L-tyrosine and for circulating-antibody formation to bacterial [Bacillus subtilis] .alpha.-amylase and the thymus-independent antigen DNP[dinitro phenol]-Ficoll was N-acetylmuramyldipeptide, MurNAc-L-Ala-D-isoGln. N-acetylmuramyldipeptide and 6-O-stearoyl-N-acetylmuramyldipeptide showed no adjuvant activity in the generation of cell-mediated cytotoxic effector cells in the spleens of C57Bl/6J mice after in vivo immunization with the allogeneic antigen mastocytoma P815-X2 cells, but N-acetylmuramyldipeptide showed adjuvant activity after in vitro sensitization of C57Bl/6J mouse spleen cells to the alloantigen mitomycin C-treated DBA/2 mouse spleen cells. 6-O-stearoylation of N-acetylmuramylpeptide could not potentiate the adjuvant activity of N-acetylmuramyldipeptide. Mitogenic and antitumor activities were not observed in N-acetylmuramyldipeptide or 6-O-stearoyl-N-acetyl-muramyldipeptide in mouse systems.