Inhibitory natural killer cell receptor (iNKR)

Inhibitory natural killer cell receptors are a group of cell surface receptors expressed on natural killer (NK) cells that primarily recognize major histocompatibility complex class I (MHC-I, also called HLA class I in humans) molecules on healthy cells and transduce negative signals to prevent NK cell-mediated cytotoxicity against normal self-cells. The main human inhibitory NK cell receptor families are the killer cell immunoglobulin-like receptors (KIRs, specifically those with long cytoplasmic tails, e.g., KIR2DL, KIR3DL), the CD94/NKG2A heterodimer, and leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1, also known as LIR-1, ILT2, CD85j). These receptors contain one or more immunoreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic domains, which recruit protein tyrosine phosphatases (such as SHP-1 and SHP-2) to counteract activating signals, maintaining immune self-tolerance and regulating cytotoxicity. Dysfunction, altered expression, or therapeutic blockade of these receptors is associated with diseases such as cancer, infection, autoimmunity, and is being explored as a strategy in cancer immunotherapy.

Other names

Inhibitory NK cell receptoriNKRHLA-specific inhibitory NK cell receptorKiller cell immunoglobulin-like receptor (KIR, inhibitory subtypes only)CD94/NKG2A receptorLeukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1, LIR-1, ILT2, CD85j)

Blockade of inhibitory NK cell receptors relieves inhibition, increasing NK cell-mediated cytotoxicity against tumor or virally infected cells. Monoclonal antibodies can block ligand binding (e.g., KIR-HLA, NKG2A-HLA-E) to enhance immune activation.