Human KIR2DL4/CD158d Antibody

KIR2DL4 (also known as 2DL4, p49, CD158d, KIR103) is a type I transmembrane protein of the killer cell Ig-like receptor (KIR) family expressed on NK and subsets of gamma deltaT and memory/effector alpha betaT cells. KIR2DL4 is a unique KIR (1-3); alleles are not clonally restricted but are expressed codominantly (4) in all activated NK cells and constitutively on CD56^hi NK cells. KIR members with two Ig-like domains (2D) usually express domains D1 and D2, but KIR2DL4 expresses D0 and D2. Other long-tailed (L) KIR have two cytoplasmic inhibitory signaling domains (ITIM), but KIR2DL4 has one ITIM and also exhibits characteristics of activating KIR (2). An arginine within the transmembrane sequence of KIR2DL4 interacts with the signaling molecule Fc epsilonRI-gamma, while in activating KIR, a transmembrane lysine interacts with DAP12 (1, 5). The KIR2DL4 gene is highly polymorphic. Seven splice variants missing one or more exons have been identified, but it is not clear whether these are expressed. Several of the nine alleles identified encode a frameshift creating a prematurely truncated protein. It is estimated that up to 25% of humans do not express KIR2DL4 capable of reaching the cell surface (1, 7, 10). Human KIR2DL4 is 65-83% amino acid identical to other primates. KIR receptors have no structural orthologs in non-primates, although mouse Ly49 proteins are functional orthologs. Cross-linking of KIR2DL4 induces NK cells to produce IFN-gamma (6, 7); stimulation with IL-2 upregulates cell surface expression on CD56^dim cells and allows cytotoxicity (7). Although a role in immune privilege of the fetus has been suggested due to reported recognition of fetal trophoblast HLA-G by KIR2DL4 in the maternal decidua (11), subsequent data have not supported this recognition (1, 9).