Killer cell immunoglobulin-like receptor (inhibitory subtype) (KIR (specifically, inhibitory KIR, e.g. KIR2DL, KIR3DL))

Killer cell immunoglobulin-like receptors (KIRs) are a highly polymorphic family of activating and inhibitory cell surface proteins expressed predominantly on natural killer (NK) cells. The inhibitory KIRs (most commonly those with long cytoplasmic tails, e.g., KIR2DL, KIR3DL) transmit inhibitory signals upon binding to specific determinants of self major histocompatibility complex (MHC) class I molecules (especially HLA-C, HLA-B, HLA-A), mediated through their immunoreceptor tyrosine-based inhibitory motifs (ITIMs). This inhibitory signaling recruits tyrosine phosphatases such as SHP-1, preventing NK cell activation and cytolysis of healthy cells, thereby maintaining self-tolerance. Loss or alteration of MHC class I molecules (as in cancer or viral infection) disrupts this inhibitory signal, permitting NK cells to eliminate diseased cells (“missing self” recognition). Inhibitory KIRs are major immune checkpoints governing NK cell function and have emerged as therapeutic targets, notably in cancer immunotherapy. The diversity of KIR genes and their HLA ligands affects disease susceptibility, transplantation outcomes, and efficacy of NK-targeted therapies[1][2][3][4][5].

Other names

Killer cell immunoglobulin-like receptorInhibitory KIRiKIRKIR2DL, KIR3DL (specific inhibitory KIRs)Immunoglobulin-like receptors (inhibitory subtype)

Antagonism or blockade of inhibitory signals to augment NK cell activity - Disruption of KIR/HLA class I interaction to facilitate NK cell-mediated lysis of tumor/virally infected cells - Immune checkpoint inhibition