KIR3DL2

KIR3DL2 is an inhibitory killer-cell immunoglobulin-like receptor with three Ig domains whose canonical ligands are the HLA-A3 and HLA-A11 allotypes. KIR3DL2 carries two cytoplasmic ITIM motifs and broadly inhibits NK-cell cytotoxicity and cytokine release when engaged by HLA-A3/A11 on target cells; it also participates in NK education through these interactions. Beyond classical HLA recognition, KIR3DL2 has gained attention for its role in pathological states: it binds HLA-B27 homodimers (misfolded dimers characteristic of ankylosing spondylitis) with high affinity on target cells and acts as a receptor for bacterial and viral antigens, scavenging extracellular human cytomegalovirus and Epstein-Barr virus particles through binding to the viral antigens, and internalizing CpG oligodeoxynucleotides, delivering them to endosomal TLR9 in NK cells and thereby promoting NK activation and survival. KIR3DL2 is aberrantly expressed on malignant T cells in Sézary syndrome and other cutaneous T-cell lymphomas, where it drives pro-survival STAT3/STAT5 signaling and serves as a therapeutic target (IPH4102/lanvitolimab antibody clinical trials).