Recombinant Human KIR3DS1/CD158e2 Fc Chimera Protein, CF

KIR3DS1 (3DS1, CD158e2) is a type I transmembrane protein that belongs to the killer cell Ig-like receptor (KIR) family. 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. Like other activating KIRs, KIR3DS1 has a short cytoplasmic tail and a positively charged amino acid (aa) within the transmembrane domain that interacts with the ITAM-bearing signaling adaptor, DAP12 (2, 4). Crosslinking of KIR3DS1 activates cytolysis and induces IFN-gamma production, confirming it to be an activating receptor (4). Approximately 38% of the population expresses KIR3DS1 on the surface of NK cells (1, 4, 5). Variants lacking the N-terminal Ig-like domain and/or with substitutions in the cytoplasmic tail have been described (1, 6). The 50 kDa, 387 aa KIR3DS1 shows 97% aa identity with KIR3DL1 within the ECD, and the two segregate as alleles (3, 7). Some activating KIRs bind weakly to the ligands recognized by their corresponding inhibitory KIR. KIR3DS1 does not bind appreciably to cells transfected with ligands for HLA-Bw4 KIR3DL1 (4, 5). However, HIV-infected people who express the combined phenotype of KIR3DS1 with Bw4 alleles that contain an isoleucine at aa 80, show delayed progression to AIDS and fewer AIDS-related opportunistic infections (7, 8). KIR receptors have no structural orthologs in nonprimates, although mouse Ly-49 proteins perform similar functions (2).