Two Human Immunodeficiency Virus Vaccinal Lipopeptides Follow Different Cross-Presentation Pathways in Human Dendritic Cells
-
Published:2003-01-15
Issue:2
Volume:77
Page:1564-1570
-
ISSN:0022-538X
-
Container-title:Journal of Virology
-
language:en
-
Short-container-title:J Virol
Author:
Andrieu Muriel1, Desoutter Jean-François1, Loing Estelle2, Gaston Jésintha1, Hanau Daniel3, Guillet Jean-Gérard1, Hosmalin Anne1
Affiliation:
1. Département d'Immunologie, Unité INSERM 567, UMR CNRS 8104, IFR 116, Institut Cochin, Paris 2. SEDAC-Therapeutics, Lille 3. EPI 99-08, Etablissement Français du Sang-Alsace, Strasbourg, France
Abstract
ABSTRACT
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 (Pol
461-484
) and another lipopeptide (Nef
66-97
) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol
461-484
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 Pol
476-484
and the HLA-A*0301-restricted Nef
73-82
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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference38 articles.
1. Albert, M. L., B. Sauter, and N. Bhardwaj. 1998. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392 : 86-89. 2. Andrieu, M., D. Chassin, J. F. Desoutter, I. Bouchaert, M. Baillet, D. Hanau, J. G. Guillet, and A. Hosmalin. 2001. Downregulation of major histocompatibility class I on human dendritic cells by HIV nef impairs antigen presentation to HIV-specific CD8+ T lymphocytes. AIDS Res. Hum. Retroviruses 17 : 1365-1370. 3. Andrieu, M., E. Loing, J. F. Desoutter, F. Connan, J. Choppin, H. Gras-Masse, D. Hanau, A. Dautry-Varsat, J. G. Guillet, and A. Hosmalin. 2000. Endocytosis of an HIV-derived lipopeptide into human dendritic cells followed by class I-restricted CD8+ T lymphocyte activation. Eur. J. Immunol. 30 : 3256-3265. 4. Anton, L. C., U. Schubert, I. Bacik, M. F. Princiotta, P. A. Wearsch, J. Gibbs, P. M. Day, C. Realini, M. C. Rechsteiner, J. R. Bennink, and J. W. Yewdell. 1999. Intracellular localization of proteasomal degradation of a viral antigen. J. Cell. Biol. 146 : 113-124. 5. Arnold-Schild, D., D. Hanau, D. Spehner, C. Schmid, H. G. Rammensee, H. de la Salle, and H. Schild. 1999. Cutting edge: receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells. J. Immunol. 162 : 3757-3760.
Cited by
40 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|