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Topical antigen application is a focus of current vaccine research. This immunization route mimics natural antigen exposure across a barrier tissue and generates T cells imprinted for skin-selective homing. Soluble antigens introduced through this route require cross-presentation by DC to generate CD8 T cell responses. Here we have explored the relative contribution of various skin-derived DC subsets to cross-priming and skin-selective imprinting. In our model, DC acquire soluble Ag  in vivo  from immunized murine skin for cross-presentation to naïve CD8 T cells  ex vivo . We find CD11b +  migratory DC to be the relevant cross-priming DC in this model. Both Langerin +  and Langerin -  CD11b +  migratory DC can cross-present antigen in our system, but only the Langerin +  subset can induce expression of the skin-selective addressin E-selectin ligand. Thus, the CD11b +  Langerin +  migratory DC population, comprised primarily of Langerhans cells, both cross-primes naïve CD8 T cells and imprints them with skin-homing capabilities.

CD11b+ Migratory Dendritic Cells Mediate CD8 T Cell Cross-Priming and Cutaneous Imprinting after Topical Immunization