Killer-cell immunoglobulin-like receptor–HLA class I interface (KIR–HLA interface)

The Killer-cell immunoglobulin-like receptor (KIR)–HLA class I interface is a critical immune checkpoint that regulates the activity of natural killer (NK) cells (Purdy & Campbell, 2009, PubMed). Inhibitory KIRs recognize specific HLA class I molecules (primarily HLA-C) on the surface of healthy cells, delivering a signal that prevents NK cell-mediated lysis (Long et al., 2013, Annual Review of Immunology). In many cancers, tumor cells exploit this mechanism by maintaining HLA expression to evade immune surveillance (Anfossi et al., 2006, Science). Therapeutic strategies targeting this interface involve monoclonal antibodies, such as lirilumab, which bind to KIRs and physically block their interaction with HLA ligands (Benson et al., 2012, Blood). By disrupting this inhibitory signal, these drugs 'release the brakes' on NK cells, enabling them to identify and destroy malignant cells (Vey et al., 2012, Blood). This target is particularly relevant in immuno-oncology and is often explored in combination with other checkpoint inhibitors like PD-1 blockers to enhance overall anti-tumor immunity (ClinicalTrials.gov).

Other names

KIR-MHC class I interfaceKIR-HLA interaction siteKiller-cell immunoglobulin-like receptor-ligand complexKIR2DL-HLA-C interface

Monoclonal antibodies target the KIR–HLA interface by binding to the extracellular domains of inhibitory KIRs (e.g., KIR2DL1/2/3), preventing their association with HLA-C ligands and thereby blocking the inhibitory signal that normally suppresses NK cell activation (Sola et al., 2009, Journal of Immunology).