Recombinant Human KIR2DL2/CD158b1 Fc Chimera Protein, CF

KIR2DL2 (2DL2, formerly NKAT6, designated CD158b) 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 CD56^dim 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, KIR2DL2 has two ITIM domains within its long tail that block activating receptor clustering (2, 5). Within the ECD, KIR2DL2 shares very high aa sequence identity (98%) with KIR2DL3. The two segregate as alleles of the same gene, although KIR2DL2 shows higher avidity for HLA‑C1 ligands (1, 6). Extracellular aa identity is also high for KIR2DL1 (92%). The three together recognize and inhibit NK cytotoxicity against cells expressing any HLA‑C allotype, allowing self‑recognition, but also conferring susceptibility to leukemia (1 ‑ 3). KIR2DL2 recognizes Asn80‑containing HLA‑C1 and, more weakly, Lys80‑containing C2 allotypes (1, 6 ‑ 8). KIR2DL2 can impact both innate and adaptive immunity, contributing to either viral persistence or antiviral immunity, depending on the HLA class I molecules expressed by the individual (9).