Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4)

Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4) is a member of the killer cell immunoglobulin-like receptor family, which are transmembrane glycoproteins expressed primarily on natural killer (NK) cells and subsets of T cells. KIR2DS4 is an activating receptor containing two immunoglobulin-like extracellular domains and a short cytoplasmic tail lacking inhibitory motifs, instead transmitting activating signals through association with the DAP12 adaptor. KIR2DS4 distinguishes itself from other KIRs by its unique specificity for certain HLA class I molecules—particularly binding some HLA-C allotypes and HLA-A*11, as well as presenting peptide specificity, which includes detection of conserved bacterial peptides. A common deletion allele yields a nonfunctional truncated form lacking HLA class I binding. Functionally, KIR2DS4 contributes to regulating NK cell responses in viral infection, cancer, and transplantation settings. KIR genes, including KIR2DS4, are highly polymorphic and their variable expression and ligand recognition can influence susceptibility to diseases and and outcomes in immune therapies[1][2][3][5].

Other names

CD158iKKA3NKAT8p58 NK receptor CL-39/CL-17Natural killer-associated transcript 8cl-39KIR-2DS4KIR1DKIR412CD158 antigen-like family member Ikiller cell immunoglobulin-like receptor, two Ig domains and short cytoplasmic tail 4p50 killer cell activating receptor KAR-K1d

Activation of NK cells by binding specific HLA class I ligands (notably some HLA-C allotypes and HLA-A*11)[1][2]. Association with DAP12 adaptor protein leads to downstream activation signaling[3]. Recognition of peptide-loaded HLA-C and HLA-A*11, including bacterial peptides, to trigger NK cell responses[1][5].