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    Team : Antigen presentation by dendritic cells


    Team leader

    Dendritic cells (DC) are the only cells that can present antigens to naive T lymphocytes and they are the main producers of type I interferons in response to viruses: they are crucial in adaptive immune responses and tolerance as well as in innate immunity.

     We first study antigen presentation pathways in human DC. We found that DC can cross-present HIV antigens to specific CD8+ T lymphocytes very efficiently not only from apoptotic, but also from live, infected CD4+ T lymphocytes. We will assess whether cross-presentation from live cells induces immunogenicity or tolerance. We have also uncovered the role of the cytosolic enzyme TPP-II in generating the C-terminus of an MHC class I-restricted HIV  epitope, a role previously ascribed only to the proteasome. We will explore the role of TPPP-II in generating the C-terminus of the same epitope processed from a lipopeptide vaccine. As current vaccine vectors show poor immunogenicity, we have set up a collaborative network together with other teams, to try and find the actions on DC that these vectors might be missing, in order to supplement them.

     We will study the microanatomy of the immune response in spleens from healthy and HIV-infected donors. We are studying the role of the different populations of DC isolated ex vivo from blood and spleen in type I IFN production and in cross-presentation.

    We are also directing another collaborative network to study the role of DC in the pathogenesis of AIDS. After uncovering the circulating DC number defect, measured by flow cytometry, in HIV+ patients, we found that type I IFN production from PBMC is dramatically impaired during primary infection. We study the correlations between plasmacytoid DC counts, Type I IFN production, T cell responses and viral replication control in different protocols. We compare HIV infection to pathogenic and non-pathogenic monkey infection models.

    Our results should help to find better vaccinal and immunotherapy protocols and predictive parameters for therapeutic decisions.