EFFECT OF A LIPOPEPTIDIC FORMULATION ON MACROPHAGE ACTIVATION AND PEPTIDE PRESENTATION TO T-CELLS

We studied a 45-69 lipopeptide obtained by N-terminal modification wit h a N-epsilon-palmitoyl lysine residue of the 45-69 peptide derived fr om the nef protein of HIV. T cells from animals immunized intraperiton eally with 45-69 lipopeptide proliferated in vitro in the presence of 45-69 peptide while no response was obtained after intraperitoneal imm unization with 45-69 peptide. The efficiency of the 45-69 lipopeptide is supported by the covalent association to the N-epsilon-palmitoyl ly sine moiety. The immunogenicity of the 45-69 lipopeptide or of the unm odified peptide is dependent on the route of immunization but is not r elated to a mitogenic effect on cells or to an increase of the peptide antigenicity. Moreover, only 45-69 lipopeptide induces the secretion of cytokines such as IL-1, IL-6 and TNF-alpha by peritoneal macrophage s. Finally, the use of 45-69 lipopeptide permits the activation of hig hly purified T cells without the addition of antigen-presenting cells. These results have implications for the formulation of synthetic vacc ines.