title: Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells.
abstract: Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery.
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Rada
authors.initials: R
authors.lastname: Ellegård
authors.forename: Adam
authors.initials: A
authors.lastname: Burgener
authors.forename: Kenzie
authors.initials: K
authors.lastname: Mogk
authors.forename: Karlhans F
authors.initials: KF
authors.lastname: Che
authors.forename: Garrett
authors.initials: G
authors.lastname: Westmacott
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D019138:Antibodies, Blocking / Q000378:metabolism; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D039641:Integrin beta Chains / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D039641:Integrin beta Chains; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; C091368:integrin beta7; D003165:Complement System Proteins