Skin-derived dendritic cells (DCs) include Langerhans cells, classical dermal DCs and a langerin-positive CD103+ dermal subset. We examined their involvement in the presentation of skin-associated viral and self antigens. Only the CD103+ subset efficiently presented antigens of herpes simplex virus type 1 to naive CD8+ T cells, although all subsets presented these antigens to CD4+ T cells. This showed that CD103+ DCs were the migratory subset most efficient at processing viral antigens into the major histocompatibility complex class I pathway, potentially through cross-presentation. This was supported by data showing only CD103+ DCs efficiently cross-presented skin-derived self antigens. This indicates CD103+ DCs are the main migratory subtype able to cross-present viral and self antigens, which identifies another level of specialization for skin DCs.