DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation.
Dendritic cells (DCs) facilitate HIV-1 spread in the host by capturing virions and transferring them to permissive lymphocytes in lymphoid organs. Lectins such as DC-specific ICAM-grabbing non-integrin (DC-SIGN) are involved in HIV-1 uptake by DCs, through high-affinity binding to viral envelope glycoproteins. We examined the role of DC-SIGN on the fate of incoming virions and on major histocompatibility complex class I (MHC-I)-restricted HIV-1 antigen presentation. We show that DC-SIGN expression in B-cell lines dramatically enhances viral internalization. In these cells, and also in primary DCs, most of the captured virions are rapidly degraded, likely in a lysosomal compartment. In addition, a fraction of incoming viral material is processed by the proteasome, leading to activation of anti-HIV-specific cytotoxic T lymphocytes (CTLs) by DC-SIGN-expressing cells. In DCs, DC-SIGN is not the only receptor involved, and redundant pathways of virus capture leading to antigen presentation likely coexist. Altogether, our results highlight new aspects of DC-SIGN interactions with HIV-1. The lectin does not significantly protect captured virions against degradation and promotes MHC-I exogenous presentation of HIV-1 antigens.
Moris
Arnaud
A
Groupe Virus et Immunité, URA CNRS 1930, Institut Pasteur, Paris, France.
Nobile
Cinzia
C
Buseyne
Florence
F
Porrot
Françoise
F
Abastado
Jean-Pierre
JP
Schwartz
Olivier
O
D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D008285:Major Histocompatibility Complex; D011956:Receptors, Cell Surface / Q000276:immunology*; D014771:Virion / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin