Insights Into Cross-Presentation

R e s e a r ch highlights

antigen presentation pDCs exposed to influenza virus for a short period of time were found to be highly effective stimulators of Prime time: insights into virus-specific CD8+ T-cell proliferation compared with myeloid DCs (mDCs). In contrast to the pathway cross-presentation characterized by Burgdorf et al., cross-presentation by pDCs did not Cross-presentation — the display presentation on MHC class I rely on proteasomal degradation of peptides derived from exogenous molecules are distinct. Based on or cytosolic transit. Instead, viral antigens on MHC class I molecules studies of mouse bone-marrow- antigens were routed directly to recy- — is important for effective derived conventional DCs (cDCs) cling endosomes containing TLR7 immune responses to tumours and presenting the soluble antigen and TLR9, which are crucial for viral infections. Although classical ovalbumin (OVA), it was found that viral recognition. The endosomes of antigen processing pathways are exogenously derived OVA transits pDCs, but not mDCs, acted as large well characterized, the pathways from endosomes into the cytosol and intracellular stores of presynthesized that lead to cross-presentation are is degraded by the proteasome before MHC class I molecules that were less clear. How can a cell physically transport to, and MHC class I load- redistributed to the cell surface early separate endogenous from exter- ing in, the same endosomes. These after exposure to influenza virus. nally derived peptides and select endosomes, identified as essential Therefore, pDCs are unique in their which are presented on MHC class cellular compartments for cross- capacity to rapidly cross-present I molecules? Two studies published presentation but not endogenous viral antigens, owing to endosomal in Nature Immunology have now antigen presentation in cDCs, con- compartments that are specialized for defined two distinct pathways for tained TAP (transporter associated viral recognition and processing. cross‑presentation in different with antigen processing), which is Together, these studies further our subsets of dendritic cells (DCs). normally found in the endoplasmic understanding of cross-presentation Burgdorf et al. report that the reticulum. Selective endosome- pathways and clarify the functional intracellular routes of endogenous specific inhibition of TAP abrogated roles of DC subsets in priming the and exogenous peptides destined for the ability of cDCs to cross-present adaptive immune response. Based OVA, but did not affect the pres- on the pDC-specific, kinetically entation of endogenous antigens. distinct pathway identified by Furthermore, signalling through Di Pucchio et al., it seems plausible Toll-like receptor 4 (TLR4) and the that cross-presentation by different adaptor protein MyD88 increased the DC subsets serves different purposes recruitment of TAP to endosomes, over the course of an infection. As thereby leading to more effective proposed by Di Pucchio et al., rapid cross-presentation by cDCs. So, this cross‑presentation by pDCs might study provides evidence for how be important for early priming of processing of endogenous and cross- memory CD8+ T-cell responses, presented antigens are mechanistically whereas priming by both mDCs and spatially separated, and suggests and pDCs at later time points that this pathway is most active under could enhance both recall and new conditions of TLR activation. responses to a pathogen. In the second article, Di Pucchio Sarah Allan et al. characterized a different pathway of cross-presentation in human ORIGINAL RESEARCH PAPERS Burgdorf, S., Schölz, C., Kautz, A., Tampé, R. & Kurts, C. plasmacytoid DCs (pDCs). pDCs Spatial and mechanistic separation of cross- are important in host defence against presentation and endogenous antigen viruses owing to their capacity to presentation. Nature Immunol. 30 March 2008 (doi:10.1038/ni.1601) | Di Pucchio, T. et al. Direct produce large amounts of type I proteasome-independent cross-presentation of interferon, but their ability to stimu- viral antigen by plasmacytoid dendritic cells on late virus-specific T-cell proliferation major histocompatibility complex class I. Nature Immunol. 30 March 2008 (doi:10.1038/ni.1602) is not well understood. In this study,