title: Cross-presentation of virus-like particles by skin-derived CD8(-) dendritic cells: a dispensable role for TAP.
abstract: Virus-like particles (VLP) induce efficient CTL responses although they do not carry any genetic information. Here, we analyzed MHC class I associated presentation of VLP-derived CTL-epitopes in vivo. After intradermal injection of VLP containing the immunodominant epitope (p33) of lymphocytic choriomeningitis virus (p33-VLP), presentation of peptide p33 in draining lymph nodes was largely restricted to CD8(-) skin-derived dendritic cells (DC). Surprisingly, and in contrast to findings with tumor cells, TAP1-deficient DC and macrophages mediated efficient cross-presentation of VLP-derived p33 in vivo and in vitro. However, the ability of TAP1-deficient DC to cross-present p33-VLP was reduced compared to wild-type DC, indicating that in DC, both TAP-dependent and TAP-independent pathways were operative. In contrast, macrophages cross-presented p33-VLP normally in the absence of TAP. The TAP-dependent pathway of cross-presentation is therefore confined to DC while both macrophages and DC harbor the TAP-independent pathway. In summary, the results show that VLP-derived epitopes are cross-presented by CD8(-) DC in vivo in a partial TAP-independent fashion and highlight important differences in the processing machinery of DC versus macrophages.
authors.affiliation: Cytos Biotechnology AG, Schlieren-Zürich, Switzerland. Ruedl@cytos.com
authors.forename: Christiane
authors.initials: C
authors.lastname: Ruedl
authors.forename: Tazio
authors.initials: T
authors.lastname: Storni
authors.forename: Franziska
authors.initials: F
authors.lastname: Lechner
authors.forename: Thomas
authors.initials: T
authors.lastname: Bächi
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000637:transplantation; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000166:cytology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D016827:CD8 Antigens; D006023:Glycoproteins; D006183:H-2 Antigens; D006512:Hepatitis B Core Antigens; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus