CLEC9a also known as DNGR-1, is a type II transmembrane glycoprotein member of the C-type lectin superfamily. Mature human CLEC9a consists of a 35aa cytoplasmic domain with an ITAM-like motif, a 21aa transmembrane segment, and a 185 extracellular domain (ECD) that contains a stalk region and one C-type lectin domain (CTLD). Within the ECD, human CLEC9a shares 57% aa sequence identity with mouse and rat CLEC9a. Although the CTLD of CLEC9a structurally resembles that of other C-type lectins, it lacks the conserved residues that typically mediate calcium and carbohydrate binding. CLEC9a is expressed as a disulfide-linked homodimer of ~45-50kD N-glycosylated subunits. Human CLEC9a expression is restricted to a subpopulation of BDCA-3+ conventional dendritic cells (cDC) and CD16- monocytes. BDCA-3+ cDC are analagous to mouse CD8+ cDC which are specialized in antigenic cross-presentation in complex with MHC class I molecules. In mouse, CLEC9a is additionally expressed on plasmacytoid dendritic cells. CLEC9a ligation enhances antigen uptake and processing, leading to presentation on MHC class I and cytotoxic T cell (CTL) priming. In mouse, CLEC9a recognizes normally intracellular determinant(s) of necrotic cells and mediates their uptake by the dendritic cell. The subsequent antigenic cross-presentation to CTL is important for clearing necrotic cellular debris. CLEC9a signaling triggers activation of the tyrosine kinase Syk.