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    Antigen cross-presentation

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    Principal investigatorAnne Hosmalin

    Mail : anne.hosmalin@inserm.fr

    Phone number : +33 1 40 51 65 06

     

    Dendritic cells (DC) are specialized in cross-presenting antigens. This function allows them to process and present, on their class I major histocompatibility molecules, antigens coming from other cells to CD8+ T lymphocytes. These  cytotoxic lymphocytes are necessary to control HIV infection or tumor growth. The specialization of DC in this function allows to present antigens from normal or infected or transformed neighboring cells, together with information that DC know how to provide, after integrating the signals from the microenvironment: start tolerance or immune responses polarized appropriately toward potential danger (infection, cancer).

    We showed or contributed to show the capacities for cross-presentation of several human DC populations: pDC, conventional DC1 bearing the XCR1 chemokine receptor, inflammatory DC.

    One particular interest of our team is cross-presentation not only from dead cells, but also from live cells. We showed that human monocyte-derived DC performed this cross-presentation from HIV-1-infected cells. With Armelle Blondel, we have extended this demonstration in vivo, where cross-presentation by bone-marrow derived DC from live cells allows a better control of metastatic B16 melanoma than cross-presentation from irradiated cells.

    Our current projects seek to establish

    -the mechanisms of antigen capture from live cells

    -the identity of the DC populations which capture antigens from live cells in vivo, in order to favor the elimination of  metastatic melanoma or HIV reservoir cells.

     

     

     Main publications

    1. Segura, E, Touzot M, Bohineust A, Cappuccio A, Chiocchia G, Hosmalin A, Dalod M, Soumelis V, and Amigorena S. Human Inflammatory Dendritic Cells Induce Th17 Cell Differentiation. Immunity, 2013; 38: 336-48
    2. Matheoud, D., Baey, C., Vimeux, L., Tempez, A., Valente, M., Louche, P., Le Bon, A., Hosmalin*, A., Feuillet*, V. Dendritic cells crosspresent antigens from live B16 cells more efficiently than from apoptotic cells and protect from melanoma in a therapeutic model. PLOS One 2011 ;6(4):e19104.
    3. Matheoud, D., Perié L., Vimeux, L., Hoeffel, G., Parent, I., Marañón, C, Bourdoncle, P., Renia, L., Blondel, A., Lucas, B., Feuillet *V., Hosmalin *, A. Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo. Blood 2010; 115 : 4412-4420  * : corresponding authors
    4. Crozat, K., Guiton*, R., Contreras*, V., Feuillet*, V., Dutertre*, C. A., Ventre, E., Vu Manh, T. P., Baranek, T., Storset, A. K., Marvel, J., Boudinot, P., Hosmalin#, A., Schwartz-Cornil#, I. and Dalod, M., The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8 + dendritic cells. * and # : equal contribution. J Exp Med. 2010 ; 207 :1283-1292.
    5. Hoeffel, G., Ripoche, AC., Matheoud, D., Nascimbeni, M., Escriou, N., Lebon, P., Heshmati, F., Guillet, Gannage, M., Caillat-Zucman, S., Casartelli, N.,  Schwartz, O., De la Salle, H., J.G., Hanau, D., Hosmalin, A. and Marañón, C. Antigen cross-presentation by human  Plasmacytoid Dendritic Cells. Immunity, 2007 ; 27 :481-492
    6. Marañón, C., Desoutter, J. F., Hoeffel, G., Cohen, W., Hanau, D., and Hosmalin, A. Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA, 2004;101:6092-6097.
    7. Seifert, U., Marañón, C., Shmueli A., Desoutter, J.F., Wesoloski, L., Janek, K., Henklein, P., Diescher, S., K., Andrieu, M., de la Salle, H., Weinschenk, T., Schild, H., Laderach, D., Galy, A., Haas, G., Kloetzel, P.M., Reiss, Y.  and Hosmalin, A. An essential role for Tripeptidyl peptidase  (TPPII) in the generation of an MHC class I epitope . Nature Immunol, 2003; 4:375-379.
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