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© Research
Publication : Immunology letters

Lipopeptide presentation pathway in dendritic cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Immunology letters - 01 Nov 2001

Hosmalin A, Andrieu M, Loing E, Desoutter JF, Hanau D, Gras-Masse H, Dautry-Varsat A, Guillet JG

Link to Pubmed [PMID] – 11595295

Immunol. Lett. 2001 Nov;79(1-2):97-100

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.

http://www.ncbi.nlm.nih.gov/pubmed/11595295