Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4)

Killer cell immunoglobulin-like receptor 2DL4 is an atypical member of the KIR family, primarily expressed in human natural killer (NK) cells and some CD8+ T cells. Unlike other KIRs, KIR2DL4 contains both activating and inhibitory signaling domains, including a single immunoreceptor tyrosine-based inhibitory motif (ITIM) and a basic residue enabling association with the FcεR-γ chain for activating signals. KIR2DL4 binds human leukocyte antigen-G (HLA-G), a non-classical HLA class I molecule predominantly expressed in fetal tissues. Functionally, engagement with HLA-G or agonistic antibodies can lead to cytokine release (notably interferon-gamma) rather than cytolytic activity, and has roles in immune tolerance during pregnancy, cancer progression, and inflammation. The receptor is unique for its intracellular signaling dynamics and possible self-association, impacting NK cell function and cellular remodeling during pregnancy. Its atypical features and disease associations make it a candidate for targeted therapies and as a diagnostic biomarker in certain cancers and immune disorders.

Other names

CD158dCD158DKIR103AS103AS15.212G9PKiller cell inhibitory receptor 103ASMHC class I NK cell receptor KIR103ASkiller cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 4killer cell inhibitory receptor 103ASKIR-2DL4KIR2DL4*00102KIR2DL4*00103KIR2DL4*00501KIR2DL4*00801KIR2DL4*00802KIR2DL4*01101KIR2DL4*021KIR2DL4*022CD158 antigen-like family member Dkiller cell immunoglobulin-like receptor 2DL4KIR103

Antagonist/agonist antibodies may modulate KIR2DL4 signaling pathways, affecting ERK phosphorylation and cell growth. The receptor's interaction with HLA-G or other ligands modulates NK cell activation/inhibition, cytokine production, and cytotoxicity.