Cross-presentation of virus-like particles by skin-derived CD8(-) dendritic cells: a dispensable role for TAP.

Journal article

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: Ruedl, C; Storni, T; Lechner, F; Bächi, T; Bachmann, M

• Publication status: Published
• Journal: European journal of immunology
• Volume: 32
• Issue: 3
• Pages: 818-825
• Publication date: 2002-03-01
• DOI: 10.1002/1521-4141(200203)32:3<818::aid-immu818>3.0.co;2-u
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Spleen; Peptide Fragments; Dendritic Cells; Antigens, CD8; Glycoproteins; Immunization; Recombinant Fusion Proteins; T-Lymphocytes; Injections, Intradermal; Mice, Transgenic; Viral Proteins; Immunodominant Epitopes; B-Lymphocytes; Mice, Knockout; Antigen Presentation; Hepatitis B Core Antigens; Receptors, Antigen, T-Cell, alpha-beta; Macrophages, Peritoneal; Antigens, Viral; H-2 Antigens; ATP-Binding Cassette Transporters; Mice; Lymph Nodes; Animals