Recombinant Human KIR2DL1/CD158a Fc Chimera Protein, CF

KIR2DL1 (2DL1, formerly NKAT1, designated CD158a) is a 348 amino acid (aa) type I transmembrane glycoprotein that belongs to the human killer cell Ig-like receptor (KIR) family (1, 2). KIRs are expressed on human CD56dim NK cells and T cell subsets, and regulate effector functions in the innate immune system (1-3). KIRs are named for the number of Ig-like domains (2D or 3D) in the extracellular domain (ECD), and whether they have long or short (L, S) cytoplasmic tails (1-3). Individuals will express varying subsets of inhibiting and activating KIRs with varying polymorphisms (1, 4). Like other inhibiting KIRs, KIR2DL1 has two ITIM domains within its long tail that block activating receptor clustering (2, 5). Within the ECD, KIR2DL1 shares high aa sequence identity (92%) with KIR2DL2. KIR2DL1 targets Lys80-containing HLA-C2 allotypes while KIR2DL2 rather recognizes Ans80 containing HLA-C1 (1, 6-8). Three KIRs proteins together (2DL1-3) recognize and inhibit NK cytotoxicity against cells expressing any HLA-C allotype, allowing self-recognition, but also conferring susceptibility to leukemia (1-3). In primary human NK cell clones, KIR2DL1 regulates the level of MHC I proteins expression required for NK cell inhibition (9).