title: Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1.
abstract: The outcome following HIV infection depends on the nature and durability of the HIV-specific T cell response induced initially. The activation of protective T cell responses depends upon dendritic cells (DC), antigen-presenting cells which have the capacity to process and present viral antigens. DC pulsed with aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune responses and promote virologic control in chronically HIV-1-infected subjects. To gain an understanding of this phenomenon, we characterized the steps involved in the presentation of antigens derived from aldrithiol-2-treated vs. infectious HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C-type lectins expressed by the DC. Inhibitor studies showed that presentation on MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner, both at the cell surface and within endosomes, and access to the classical endosomal processing pathway. MHC class II presentation of HIV-associated antigens was dependent on active endocytosis, probably receptor-mediated, and subsequent degradation of virions in acidified endosomes in the DC. Our study brings forth new facts regarding the binding, uptake, and processing of chemically inactivated virions leading to efficient antigen presentation and should aid in the design of more effective HIV vaccines.
authors.affiliation: Department of Medicine and Pathology, School of Medicine, New York University, NY, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Sabado
authors.forename: Ethan
authors.initials: E
authors.lastname: Babcock
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Kavanagh
authors.forename: Veronica
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D004220:Disulfides / Q000494:pharmacology; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D014771:Virion / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D004220:Disulfides; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl