mCLEC9a MAb (Cl 7005 (25 ug)

Background: CLEC9a

CLEC9a (C-type lectin domain family 9 member A), also known as DNGR-1, is a type II transmembrane glycoprotein member of the C-type lectin superfamily. 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 approximately 50 kDa 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. Alternative splicing of mouse CLEC9a generates isoforms with deletions in the transmembrane segment, stalk region, or CTLD. Within aa 57-264 of the ECD, mouse CLEC9a shares 57% and 80% aa sequence identity with human and rat CLEC9a, respectively.