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Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-06-1801. This Article Full Text (PDF) All Versions of this Article: 2003-06-1801v1 102/13/4448    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fonteneau, J. F. Articles by Larsson, M. Search for Related Content PubMed PubMed Citation Articles by Fonteneau, J. F. Articles by Larsson, M. Social Bookmarking                   What's this? Submitted June 6, 2003 Accepted August 11, 2003 Characterization of the MHC class I crosspresentation pathway for cell associated antigens by human dendritic cells Jean Francois Fonteneau, Daniel G Kavanagh, Margareta Lirvall, Catherine Sanders, Timothy L Cover, Nina Bhardwaj, and Marie Larsson* Institute de Biologie, INSERM U463 44093, Nantes, France School of Medicine, New York University, New York, NY, USA Department of Cell Biology, University of Linkoping, Linkoping, Sweden Graduate School of Art and Science, Emory University, Atlanta, USA Department of Medicine and Microbiology and Immunology, Vanderbilt University School of Medicine and VAMC, Nashville, USA * Corresponding author; email: larssom{at}mail.rockefeller.edu. MHC class I presentation of exogenous antigens is the mechanism enabling professional APCs to induce CD8+ T cell responses against viruses and tumors that do not have access to the classical MHC class I pathway. We have characterized the uptake, processing and MHC class I crosspresentation by human dendritic cells (DCs) of cell-associated antigens derived from physiologically relevant sources, namely vaccinia virus-infected apoptotic and necrotic cells. We show that cross-presentation is a rapid process, detectable within 2-4 h after uptake of dead cells, and that proteolysis by Cathepsin D in an acidic endosomal compartment is essential for crosspresentation. The presentation is abolished when the cells phagocytic or macropinocytic functions are inhibited, and is TAP dependent, brefeldin A sensitive and requires functional proteasomes. Altogether these data suggest that antigens derived from apoptotic and necrotic cells require access to the cytosol to intersect with the conventional MHC class I pathway for presentation of cytosolic proteins. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Wang, T. Uto, T. 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