Article abstract
Nature Immunology 9, 558 - 566 (2008)
Published online: 30 March 2008 | doi:10.1038/ni.1601
Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation
Sven Burgdorf1, Christian Schölz2, Andreas Kautz1, Robert Tampé2 & Christian Kurts1
Abstract
Antiviral or antitumor immunity requires activation of cytotoxic CD8+ T cells by dendritic cells, which present viral or tumor antigens on major histocompatibility complex (MHC) class I molecules. The intracellular mechanisms facilitating MHC class I–restricted presentation of extracellular antigens ('cross-presentation') are unclear. Here we demonstrate that cross-presentation of soluble antigen occurred in an early endosomal compartment distinct from the endoplasmic reticulum where endogenous antigen is loaded onto MHC class I. Efficient cross-presentation required endotoxin-induced, Toll-like receptor 4– and signaling molecule MyD88–dependent relocation of the transporter associated with antigen processing, essential for loading of MHC class I, to early endosomes. Transport of cross-presented antigen from endosomes to the cell surface was inhibited by primaquine, which blocks endosomal trafficking. Thus, cross-presentation is spatially and mechanistically separated from endogenous MHC class I–restricted antigen presentation and is biased toward antigens containing microbial molecular patterns.
- Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms University, 53105 Bonn, Germany.
- Institute of Biochemistry, Biocenter, Johann Wolfgang Goethe University, 60438 Frankfurt am Main, Germany.
Correspondence to: Sven Burgdorf1 e-mail: sven.burgdorf@ukb.uni-bonn.de
Correspondence to: Christian Kurts1 e-mail: ckurts@web.de
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