This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andrieu, M.
Right arrow Articles by Hosmalin, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andrieu, M.
Right arrow Articles by Hosmalin, A.

 Previous Article  |  Next Article 

Journal of Virology, January 2003, p. 1564-1570, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1564-1570.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Two Human Immunodeficiency Virus Vaccinal Lipopeptides Follow Different Cross-Presentation Pathways in Human Dendritic Cells

Muriel Andrieu,1 Jean-François Desoutter,1 Estelle Loing,2 Jésintha Gaston,1 Daniel Hanau,3 Jean-Gérard Guillet,1 and Anne Hosmalin1*

Département d'Immunologie, Unité INSERM 567, UMR CNRS 8104, IFR 116, Institut Cochin, Paris,1 SEDAC-Therapeutics, Lille,2 EPI 99-08, Etablissement Français du Sang-Alsace, Strasbourg, France3

Received 19 August 2002/ Accepted 15 October 2002

An efficient vaccine against human immunodeficiency virus (HIV) must induce good cellular immune responses. To do this, it must be processed and presented by dendritic cells, which are required for primary T-lymphocyte stimulation. We have previously shown that a model lipopeptide containing a short epitopic peptide from HIV-1 was endocytosed and presented in association with major histocompatibility complex class I molecules by human dendritic cells to specific CD8+ T lymphocytes, but the cross-presentation pathway needed to be precisely determined. We have studied a longer lipopeptide (Pol461-484) and another lipopeptide (Nef66-97) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol461-484 lipopeptide was internalized by endocytosis, as assessed by confocal microscopy. The lipopeptides were processed by dendritic cells and presented to CD8+ T cells specific for the HLA-A*0201-restricted Pol476-484 and the HLA-A*0301-restricted Nef73-82 epitope, respectively. Presentation of both lipopeptides was inhibited by brefeldin A. Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome-specific inhibitor, but not by monensin. This shows that it gained access to the cytosol to be digested by the proteasome. In contrast, presentation of the Nef lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a classical inhibitor of acid-dependent endosomal enzyme activity, indicating an endocytic processing pathway yielding to major histocompatibility complex class I-restricted presentation. Therefore, the two lipopeptides followed different cross-presentation pathways, both resulting in efficient presentation to CD8+ T lymphocytes.

* Corresponding author. Mailing address: Antigen Presentation by Dendritic Cell Research Group, Immunology Department, Cochin Institute, BÂtiment Gustave Roussy, 8ème Étage, 27 rue du Faubourg St-Jacques, 75014 Paris, France. Phone: 33 1 40 51 65 06. Fax: 33 1 40 51 65 35. E-mail: hosmalin{at}cochin.inserm.fr.

Journal of Virology, January 2003, p. 1564-1570, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1564-1570.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»