KIR3DL1 is a member of the killer cell immunoglobulin-like receptor (KIR) family, primarily expressed on natural killer (NK) cells and certain T-cell subsets. As an inhibitory receptor, it plays a critical role in regulating NK cell-mediated immune responses by interacting with specific human leukocyte antigen (HLA) class I molecules, particularly HLA-Bw4 epitopes. This interaction delivers inhibitory signals to prevent NK cell activation, ensuring immune tolerance to healthy cells while enabling targeted cytotoxicity against infected or malignant cells lacking HLA expression.
The KIR3DL1 gene exhibits extensive polymorphism, with over 100 alleles identified, contributing to diverse receptor expression levels and functional variations across populations. This genetic diversity influences susceptibility to diseases and clinical outcomes. For instance, specific KIR3DL1/HLA-B combinations are associated with delayed HIV progression, control of viral infections, and altered risks for autoimmune disorders and cancers. In hematopoietic stem cell transplantation, KIR3DL1-ligand mismatching may enhance graft-versus-leukemia effects but also increase graft-versus-host disease risks.
Antibodies targeting KIR3DL1 have been developed to modulate NK cell activity for therapeutic purposes. Blocking these inhibitory receptors can enhance NK-mediated tumor cell lysis, offering potential in cancer immunotherapy. Conversely, agonist antibodies may suppress excessive NK activation in autoimmune conditions. Research continues to explore their clinical applications, balancing efficacy with immune-related adverse effects.