Submitted February 28, 2006
Accepted April 26, 2006
Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T cell activation, viral transfer
Arnaud Moris, Anthony Pajot, Fabien Blanchet, Florence Guivel-Benhassine, Margarita Salcedo, and Olivier Schwartz*
Groupe Virus et Immunite, URA CNRS
Unite d Immunite Cellulaire Antivirale, Institut Pasteur
IDM Research Laboratories, Institut des Cordeliers
* Corresponding author; email: schwartz{at}pasteur.fr.
Human immunodeficiency virus (HIV)-specific CD4+ lymphocytes are preferentially infected in HIV-positive individuals. To study this preferential infection, we have derived several HIV-specific (HS) CD4+ clones. We show that in Dendritic Cells (DCs), HIV virion capture lead to Major Histocompatibility Complex class-II (MHC-II)-restricted viral antigen presentation, and to activation of HS cells. In contrast, neither cell-free virions nor infected lymphocytes activated HS cells. In DCs, the Dendritic Cell-Specific Intercellular adhesion molecule 3-Grabbing Nonintegrin (DC-SIGN/CD209), which internalizes virions, promoted MHC-II presentation of HIV antigens. Activation of HS cells by HIV-exposed DCs triggered an efficient viral spread in lymphocytes. CD4+ clones with irrelevant antigenic specificities were not activated by HIV-exposed DCs, and poorly supported viral replication under this setting. Our results unravel the mechanisms of MHC-II-restricted HIV antigen presentation by DCs, and describe how HIV gains access to the very cells designed by the immune system to counteract this pathogen.
