Differential uptake and cross-presentation of human papillomavirus virus-like particles by dendritic cells and Langerhans cells.

A causal link between cervical cancer and high-risk human papillomaviruses has been established. The virus infects basal cells of the mucosa, where Langerhans cells are the resident antigen-presenting cells. Langerhans cells and dendritic cells, which are targeted by vaccination, internalize similar amounts of human papillomavirus virus-like particles (VLPs), albeit through different uptake mechanisms. VLP uptake by dendritic cells results in activation and cross-presentation of MHC class I-restricted peptides with costimulation to T cells. Conversely, VLP uptake by Langerhans cells leads to cross-presentation in the absence of costimulation. Efficient VLP cross-presentation by Langerhans cells with costimulation can be achieved by addition of CD40 ligand. The lack of a protective immune response after viral contact with Langerhans cells may explain why some women fail to mount an immune response against the virus or why the immune responses that do develop may allow the virus to persist. Because VLPs are currently being tested as a vaccine against cervical cancer, our data are very topical and have implications for optimal vaccination strategies against this disease.