Burgdorf Sven, Schölz Christian, Kautz Andreas, Tampé Robert, Kurts Christian
Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms University, 53105 Bonn, Germany.
Nat Immunol. 2008 May;9(5):558-66. doi: 10.1038/ni.1601. Epub 2008 Mar 30.
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.
抗病毒或抗肿瘤免疫需要树突状细胞激活细胞毒性CD8 + T细胞，树突状细胞在主要组织相容性复合体（MHC）I类分子上呈递病毒或肿瘤抗原。促进MHC I类限制的细胞外抗原呈递（“交叉呈递”）的细胞内机制尚不清楚。在这里，我们证明可溶性抗原的交叉呈递发生在一个早期内体区室中，该区域不同于内质网，在内质网中内源性抗原被加载到MHC I类分子上。高效的交叉呈递需要内毒素诱导的、Toll样受体4和信号分子MyD88依赖性的与抗原加工相关的转运体重新定位，这对于MHC I类分子的加载至关重要，转运体重新定位到早期内体。伯氨喹抑制交叉呈递的抗原从内体到细胞表面的运输，伯氨喹可阻断内体运输。因此，交叉呈递在空间和机制上与内源性MHC I类限制的抗原呈递分开，并且偏向于含有微生物分子模式的抗原。
