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Nat Immunol. 2008 May;9(5):558-66. doi: 10.1038/ni.1601. Epub 2008 Mar 30.

Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation.

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  • 1Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms University, 53105 Bonn, Germany. sven.burgdorf@ukb.uni-bonn.de

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.

PMID:
18376402
[PubMed - indexed for MEDLINE]
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