Dendritic cells (DCs) are the most potent professional APC, with a unique capacity to initiate primary immune responses, activating effector CD4+ and cytotoxic CD8+ T cells, a capacity that is not shared with other APCs. For CTL induction, the classical pathway to charge MHC class I molecules (MHC I) implies expression of antigen in the cytosol of APC. An alternative approach is offered by the unique property of APCs to cross-prime a CTL response against exogenous antigens. Indeed, DCs have the very particular ability to cross-present exogenous particulate or cell-associated antigens. Virus-like particles (VLPs) have shown a remarkable ability to deliver antigens in vivo into the DC MHC class I pathway and also to induce powerful prophylactic as well as therapeutic immune responses against tumor or viral challenges, due to their capacity to stimulate cytotoxic CD8+ T cells. The particular efficacy of VLPs to induce CTL responses is explained by their ability to target DCs in vivo and by their capacity to trigger DCs maturation. Using recombinant porcine parvovirus virus-like particles (PPV-VLPs) as a model of exogenous antigen, we have studied the role of different spleen DC subpopulations in the in vivo and in vitro capture, processing and capture of PPV-VLPs. We have found that all DC subpopulations present in murine spleen are able to present PPV-VLPs. However, there exist several differences between DCs sub-populations, which will be discussed during the lecture. DCs process PPV-VLPs following a route known as from endosome-to-cytosol. We have also observed that the high immunogenicity of PPV-VLPs is linked to their capacity to activate DCs, including expression of costimulatory molecules, cytokines and chemokines, in a CD4 T cell independent manner. More exhaustive studies will be necessary in order to reveal the features of the VLPs processing pathways and to take advantage of them for the design of optimized vaccines.
