title: Hepatitis B virus-like particles access major histocompatibility class I and II antigen presentation pathways in primary dendritic cells.
abstract: Virus-like particles (VLPs) represent high density displays of viral proteins that efficiently trigger immunity. VLPs composed of the small hepatitis B virus envelope protein (HBsAgS) are useful vaccine platforms that induce humoral and cellular immune responses. Notably, however, some studies suggest HBsAgS VLPs impair dendritic cell (DC) function. Here we investigated HBsAgS VLP interaction with DC subsets and antigen access to major histocompatibility complex (MHC) class I and II antigen presentation pathways in primary DCs. HBsAgS VLPs impaired plasmacytoid DC (pDC) interferon alpha (IFNα) production in response to CpG in vitro, but did not alter conventional DC (cDC) or pDC phenotype when administered in vivo. To assess cellular immune responses, HBsAgS VLPs were generated containing the ovalbumin (OVA) model epitopes OVA(257-264) and OVA(323-339) to access MHCI and MHCII antigen presentation pathways, respectively; both in vitro and following immunisation in vivo. HBsAgS VLP-OVA(257-264) elicited CTL responses in vivo that were not enhanced by inclusion of an additional MHCII helper epitope. HBsAgS VLP-OVA(257-264) administered in vivo was cross-presented by CD8(+) DCs, but not CD8(-) DCs. Therefore, HBsAgS VLPs can deliver antigen to both MHCI and MHCII antigen presentation pathways in primary DCs and promote cytotoxic and helper T cell priming despite their suppressive effect on pDCs.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3010, Australia.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Moffat
authors.forename: Wan-Shoo
authors.initials: WS
authors.lastname: Cheong
authors.forename: José A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Netter
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D016898:Interferon-alpha / Q000276:immunology; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; C118669:S envelope protein, hepatitis B virus; D014759:Viral Envelope Proteins; D010047:Ovalbumin