Cellular immune responses induced by in vivo priming with a lipid-conjugated multimeric antigen peptide.
This report investigates the generation of cytotoxic T lymphocytes (CTL) by in vivo administration of a synthetic antigen linked to a lipid moiety, tripalmitoyl-S-glyceryl cysteine (P3C). The antigen consisted of a 17-mer peptide, derived from the gp120 envelope protein of the human immunodeficiency virus type-1 (HIV-1), in a tetravalent multiple antigenic peptide (MAP) configuration. A single injection of MAP-P3C elicited a long-lasting CTL response in mice. The route of administration was not a determining factor, since intravenous (i.v.) and intraperitoneal (i.p.) priming were both effective. The HIV strain-specific cytotoxic lymphocytes were of the CD8+ subset and class I restricted. A broad cytolytic activity could be achieved by priming with a mixture of homologous peptides from gp120 IIIB and MN strains. Following the administration of the monoclonal antibody GK1.5, resulting in the depletion of the CD4+ T-lymphocyte subpopulation, mice were able to mount a strong CTL response. This finding demonstrates that in priming with a peptide antigen covalently linked to a lipid, such as MAP-P3C, CD4+ cells are not required for the generation of CD8+ cytotoxicity. In contrast, the elimination of macrophages by the carrageenan pretreatment caused suppression of the T-cell lytic activity, suggesting a substantial contribution of the phagocytic cells in mounting CTL response. Taken together, these results may lead to new strategies in designing a human immunodeficiency virus type-1 (HIV-1) vaccine based on synthetic peptides.
Nardelli
B
B
Dept. of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232-2363.
Tam
J P
JP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D003545:Cysteine / Q000031:analogs & derivatives* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
D016827:CD8 Antigens; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C038837:tripalmitoyl cysteine; D003545:Cysteine