KIR3DL1

KIR3DL1 is an inhibitory killer-cell immunoglobulin-like receptor with three extracellular Ig domains (D0-D1-D2) that recognizes HLA-B molecules carrying the Bw4 serological epitope (residues 77-83 on the HLA-B α1 helix), and additionally HLA-A alleles with Bw4 motifs such as HLA-A*23/*24. KIR3DL1's long cytoplasmic tail contains two ITIMs that recruit SHP-1/SHP-2, inhibiting NK cytotoxicity upon ligand engagement; it is one of the principal mediators of NK-cell education, calibrating functional competence against the density of Bw4+ HLA-B. The KIR3DL1-HLA-Bw4 axis is famous in HIV biology: compound genotypes of high-expression KIR3DL1 alleles with isoleucine-80 Bw4 ligands (e.g., HLA-B*57) slow progression to AIDS, through education of NK cells that become potent HIV-infected cell killers; KIR3DS1, its activating allelic counterpart, requires the same ligand for protective effects. KIR3DL1 polymorphism is extensive (over 60 alleles), affecting surface expression levels and ligand affinity, which influences susceptibility to viral infections, outcomes of hematopoietic stem-cell transplantation, preeclampsia and psoriatic arthritis.