**2. Conventional dendritic cells 1 (cDC1)**

cDC1s constitute ~0.03% of PBMCs and are found in the blood, tonsil, spleen and non-lymphoid tissues such as the skin. They were classically defined by the high expression of CD141 (blood DC antigen 3 (BDCA3) or thrombomodulin) [10]. However, CD141 is not a completely specific marker for cDC1 as it is also expressed on endothelial cells, monocytes and other DC subsets [8]. Using phenotypic, transcriptional and functional assays, these CD141+ DCs have been further characterised as CD11c<sup>+</sup> HLA-DR+ CD11b<sup>−</sup>CD172a<sup>−</sup> CLEC9a+ XCR1+ Necl2+ cells that lack monocytic markers CD14 and CD16 [4, 11] identifying them as human cDC1 [12–16].

The dependence of CD141<sup>+</sup> DCs on Flt3 ligand (FL), an important DC developmental factor, has been demonstrated *in vitro* and *in vivo* [11, 17–19] and transcription factor *BATF3* is required *in vitro* but not *in vivo* [15]. Another cDC1-defining transcription factor, *IRF8*, is also highly expressed in human cDC1, although patients harbouring mutations in *IRF8* did not exhibit cDC1 deficiencies, suggesting the involvement of other transcription factors as well [6, 20]. Furthermore, genome wide expression profiling and microarray analyses have revealed transcriptional profile clustering between CD141+ DCs in blood and non-lymphoid tissues, as well as between human blood CD141+ DCs and murine CD8a<sup>+</sup> and migratory CD103+ DCs [4, 21], firmly establishing CD141+ cDC as cDC1.

PRRs expressed by human cDC1s are predominantly Toll-like receptor (TLR) 3, located in endosomes and which recognises double-stranded RNA and TLR8, also located in endosomes and which recognises bacterial ssRNA and mammalian mitochondrial RNA [10, 22]. In response to TLR3 signals [23] and also HCV *in vivo* [23, 24], the cDC1 produce large amounts of type III interferon (IFN), also known as IFN-lambda (λ).

The cDC1s are superior to other DC subsets in their ability to present ex*ogenous* Ag on MHCI, a process known as cross-presentation [2] and the activation of cytotoxic CD8+ T cells, crucial for anti-tumour responses. In particular, they have a specialised ability to cross-present Ags from dead or necrotic cells to CD8+ T cells, enhanced by Clec9a on cDC1 binding to actin filaments exposed on dead and dying cells [25]. The cDC1 are superior at inducing Th1 differentiation of CD4 helper T cells [11, 16].
