title: Lipopeptide presentation pathway in dendritic cells.
abstract: Lipopeptides are currently being evaluated as candidate vaccines in human volunteers. They elicit cytotoxic responses from CD8(+) T lymphocytes, whereas peptides without a lipidic moiety usually do not. The exact processing and presentation pathways leading to association with MHC class I molecules has not yet been defined. This is of particular interest in dendritic cells, which are required for primary T cell stimulation. We have tracked lipopeptides derived from an HLA-A2.1-restricted HIV-1 Reverse Transcriptase epitope, by N-terminal addition of an N-epsilon-palmitoyl-lysine. Entry of the lipopeptides into human monocyte-derived dendritic cells (MDC) was mediated by endocytosis, as assessed by colocalization using analogs labelled with rhodamine, and by confocal microscopy. This internalization in DC induced functional stimulation of CD8(+) T lymphocytes specific for the epitopes, quantified by Interferon-gamma ELISPOT assays. The peptide alone was not visualized inside the DC and was only presented through direct surface association to HLA-A*0201. Therefore, lipopeptides provide a model system to define precisely the cross-presentation pathways that lead exogenous proteins to associate with class I MHC molecules within dendritic cells. Using this approach, cross-presentation pathways can be better defined and vaccine lipopeptides can be further optimized for MHC class I association in human dendritic cells.
authors.affiliation: INSERM U445, ICGM, 27 rue du Faubourg St-Jacques 75014, Paris, France. hosmalin@cochin.inserm.fr
authors.forename: A
authors.initials: A
authors.lastname: Hosmalin
authors.forename: M
authors.initials: M
authors.lastname: Andrieu
authors.forename: E
authors.initials: E
authors.lastname: Loing
authors.forename: J F
authors.initials: JF
authors.lastname: Desoutter
authors.forename: D
authors.initials: D
authors.lastname: Hanau
authors.forename: H
authors.initials: H
authors.lastname: Gras-Masse
authors.forename: A
authors.initials: A
authors.lastname: Dautry-Varsat
authors.forename: J G
authors.initials: JG
authors.lastname: Guillet
mesh_terms: D016915:AIDS Vaccines / Q000494:pharmacology; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015789:HLA-A2 Antigen; D008074:Lipoproteins; D010446:Peptide Fragments; D054303:HIV Reverse Transcriptase