Recombinant Human KIR2DS4/CD158i Fc Chimera Protein, CF

KIR2DS4 (2DS4), previously called NKAT-8 and designated CD158i, is a type I transmembrane glycoprotein that belongs to the killer cell Ig-like receptor (KIR) family (1). KIRs are expressed on CD56^dim NK cells and T cell subsets where they differentiate normal from abnormal cells 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. KIR2DS4 cDNA encodes 304 amino acids (aa) including a 21 aa signal sequence, a 224 aa ECD, a 20 aa transmembrane sequence and a 39 aa cytoplasmic domain. KIR receptors have no structural orthologs in nonprimates, although mouse Ly-49 proteins perform similar functions (2). Like other activating KIRs, KIR2DS4 has a short tail and a positively charged amino acid (aa) within the transmembrane domain that interacts with the ITAM-bearing signaling adaptor, DAP12 (2, 3). Expression of activating KIR is balanced with inhibitory KIR to impart specificity to the immune response. KIR2DS4 recognizes six HLA-C allotypes and two HLA-A allotypes (A*1101 and A*1102) but no HLA-B allotypes (4, 5). It has also been suggested that KIR2DS4 recognizes a non-MHC ligand, based on specific binding to melanoma cells that lack MHC Class I (6). A common allele, KIR2DS4*003, is present in up to 89% of Caucasians and ~30% of Asians; it creates a prematurely terminated, soluble, inactive form (7, 8). Lack of functional KIR2DS4 can potentially create unbalanced inhibition of killer cell function (4, 8).