Inhibitory killer cell immunoglobulin-like receptor (KIR) (KIR)

Inhibitory killer cell immunoglobulin-like receptors (KIRs) are a diverse family of type I transmembrane glycoproteins expressed primarily on natural killer (NK) cells and certain T cell subsets [1.3.1, 1.4.1]. These receptors play a fundamental role in the innate immune system by monitoring the expression of major histocompatibility complex (MHC) class I molecules, such as HLA-A, HLA-B, and HLA-C, on the surface of nucleated cells [1.1.2, 1.3.2]. Under normal conditions, the binding of inhibitory KIRs to self-MHC molecules triggers an inhibitory signal via immunoreceptor tyrosine-based inhibitory motifs (ITIMs), preventing NK cells from attacking healthy tissues [1.1.1, 1.4.1]. However, many tumors and virally infected cells exploit this mechanism by maintaining MHC expression to evade immune surveillance, or conversely, NK cells may fail to recognize cells that have downregulated MHC (the 'missing self' hypothesis) [1.3.1, 1.4.2]. Therapeutic strategies, such as the use of monoclonal antibodies like lirilumab, aim to block these inhibitory KIRs to enhance NK cell-mediated cytotoxicity against cancer cells [1.2.1, 1.4.2]. The extensive genetic polymorphism of the KIR locus contributes to significant inter-individual variability in immune responses, making KIRs important factors in disease susceptibility, transplantation outcomes, and the efficacy of immunotherapy [1.3.2, 1.3.3].

Other names

CD158Killer cell inhibitory receptoriKIRKIR2DLKIR3DL

Blockade of inhibitory KIR receptors to prevent the suppression of Natural Killer (NK) cell activity by MHC class I molecules, thereby enhancing anti-tumor immune responses.