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 with a N epsilon-palmitoyl lysine residue of the 45-69 peptide derived from the nef protein of HIV. T cells from animals immunized intraperitoneally with 45-69 lipopeptide proliferated in vitro in the presence of 45-69 peptide while no response was obtained after intraperitoneal immunization with 45-69 peptide. The efficiency of the 45-69 lipopeptide is supported by the covalent association to the N epsilon-palmitoyl lysine moiety. The immunogenicity of the 45-69 lipopeptide or of the unmodified peptide is dependent on the route of immunization but is not related 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 macrophages. Finally, the use of 45-69 lipopeptide permits the activation of highly purified T cells without the addition of antigen-presenting cells. These results have implications for the formulation of synthetic vaccines.
Centre d'Immunologie des Maladies Transmissibles et Allergiques, Unité mixte INSERM U167-CNRS 624, Lille, France.
F
F
Rouaix
H
H
Gras-Masse
C
C
Mazingue
E
E
Diesis
P R
PR
Ridel
J
J
Estaquier
A
A
Capron
A
A
Tartar
C
C
Auriault
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000096:biosynthesis; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007114:Immunization; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008262:Macrophage Activation; D008297:Male; D008969:Molecular Sequence Data; D015394:Molecular Structure; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification; D054311:nef Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D015693:Gene Products, nef; D008074:Lipoproteins; D014614:Vaccines, Synthetic; D054311:nef Gene Products, Human Immunodeficiency Virus