Cellular mechanisms governing cross-presentation of exogenous antigens

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The recent discovery of fusion of endoplasmic reticulum membrane with nascent phagosomes suggests that this peripheral compartment in macrophages and dendritic cells may serve as an organelle optimized for major histocompatibility complex (MHC) class I–restricted cross-presentation of exogenous antigens. The process allows intersection of the endosomal system with the endoplasmic reticulum, the classical site of MHC class I peptide loading, and may reconcile the seemingly conflicting evidence indicating both of these sites are crucial in cross-presentation. Here we discuss the potential mechanisms involved in loading exogenous antigens onto MHC class I molecules and the implications of this new evidence for the in vivo function of dendritic cells.

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Figure 1: MHC class I peptide-loading complex.
Figure 2: Sec61p, the probable gateway from the ER to the cytosol used in the degradation of misfolded glycoproteins, and the peptide-loading complex are recruited to phagosomes by ER-mediated phagocytosis.
Figure 3: Two models of cross-presentation.


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We thank N. Dometios for help in preparing the manuscript. Supported by the Howard Hughes Medical Institute and by National Institutes of Health (F31 AI 101347 to A.L.A.).

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Correspondence to Peter Cresswell.

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Ackerman, A., Cresswell, P. Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol 5, 678–684 (2004) doi:10.1038/ni1082

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