Inhibitory Natural Killer cell receptors (iNKRs)

Inhibitory Natural Killer (NK) cell receptors are a group of surface proteins that regulate the activation threshold of NK cells and certain T cell subsets to ensure self-tolerance. The primary members include the Killer-cell Immunoglobulin-like Receptor (KIR) family (e.g., KIR2DL1, KIR3DL1) and the CD94/NKG2A heterodimer, which recognize specific HLA class I molecules (HLA-A, B, C, and E) on target cells (Source: UniProt, P43626; P26715). Upon binding their ligands, these receptors signal through cytoplasmic Immunoreceptor Tyrosine-based Inhibitory Motifs (ITIMs) to recruit phosphatases that counteract activating signals (Source: PubMed, PMID: 11244035). In the tumor microenvironment, the upregulation of HLA class I molecules or the presence of these inhibitory receptors on tumor-infiltrating lymphocytes serves as a mechanism of immune evasion (Source: PubMed, PMID: 30503213). Therapeutic antibodies like monalizumab and lirilumab are designed to block these interactions, effectively acting as checkpoint inhibitors for the innate immune system to enhance anti-tumor cytotoxicity (Source: PubMed, PMID: 28468904).

Other names

Inhibitory Killer-cell immunoglobulin-like receptorsInhibitory KIRsNKG2ACD94/NKG2ALILRB1ILT2MHC class I-specific inhibitory receptors

Blockade of inhibitory signaling by preventing the interaction between inhibitory NK receptors and their HLA class I ligands, thereby promoting NK cell and T-cell mediated lysis of tumor cells (Source: PubMed, PMID: 28468904).