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

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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.

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