Abstract
The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells. We then discuss the role of cDC1s as a cellular platform to combine antigen processing for class I and class II MHC presentation to allow the integration of “help” from CD4 T cells during priming of CD8 T cell responses.
Highlights
Dendritic cells (DCs) are a distinct lineage of innate immune cells that was originally defined based on its unique stellate morphology and ability to prime T cell responses[1,2,3]
DCs broadly segregate into four groups, plasmacytoid DCs, classical DCs, Langerhans cells, and monocyte-derived DCs based on function and surface markers. plasmacytoid dendritic cell (pDC) are potent producers of type I interferons in response to viral pathogens4–7. classical dendritic cell (cDC) themselves are divided into two lineages, recently renamed[8] as cDC1 (CD8α+ DCs) and cDC2 (CD8α- DCs)
Recent imaging studies suggest that cDC1s function as a platform for CD4 T cell help during viral infections[74,78], likely through CD40–CD40L interactions[84,85]
Summary
Dendritic cells (DCs) are a distinct lineage of innate immune cells that was originally defined based on its unique stellate morphology and ability to prime T cell responses[1,2,3]. CDC1 cells require the Irf[810,15,16] and Batf[3] transcription factors[10,16,17] and produce the IL-12 necessary for protection against Toxoplasma gondii[18,19] They are the subset involved in priming CD8 T cell responses to tumors and virally infected cells through cross-presentation[17,20]. DCs that resemble splenic cDC1 and cDC2 by surface markers can be generated in large numbers in bone marrow cultures with Flt3L34,35 These cells are able to present antibody-targeted antigens and activate T cells to a similar extent as cDCs of the same lineage derived in vivo[36]. Examining molecules described in moDCs in cDC1s and studying other cDC1-specific genes will aid in our understanding of how cross-presentation against viral and cancer antigens occurs and may provide more insight into whether moDCs are a true DC subset in vivo. Grant information The author(s) declared that no grants were involved in supporting this work
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