Killer cell immunoglobulin-like receptor–Human leukocyte antigen class I interaction (KIR–HLA class I)

The interaction between Killer cell Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) class I molecules is a fundamental regulatory axis of the innate immune system [3, 5]. Inhibitory KIRs, expressed primarily on natural killer (NK) cells and some T cells, recognize specific HLA-A, -B, or -C alleles on healthy cells to maintain self-tolerance and prevent auto-aggression [3, 11]. In the context of oncology, many tumors exploit this mechanism by maintaining HLA expression to deliver inhibitory signals that suppress NK cell-mediated surveillance [1, 10]. Therapeutic targeting of this interaction involves monoclonal antibodies, such as lirilumab, which block the binding of inhibitory KIRs to their HLA ligands [2, 8]. This blockade effectively "releases the brakes" on NK cells, enhancing their ability to identify and eliminate malignant or infected cells [1, 10]. Beyond cancer, this interaction is critical in viral infections, reproduction, and the success of hematopoietic stem cell transplantations [4, 7, 13]. The genetic diversity of both KIR and HLA loci makes this interaction highly variable across individuals, significantly influencing disease susceptibility and treatment response [9, 12].

Other names

KIR-HLA axisKIR-MHC class I interactionKiller cell immunoglobulin-like receptor-MHC class I interactionKIR-HLA-C interaction

Blockade of inhibitory KIR receptors (such as KIR2DL1/2/3) to prevent their interaction with HLA class I ligands (primarily HLA-C), thereby removing the inhibitory signal and activating natural killer (NK) cells and certain T cell subsets to eliminate target cells [1, 2, 10].