Killer-cell immunoglobulin-like receptor and Killer cell lectin-like receptor subfamily C member 1 (KIR/NKG2A)

Killer-cell immunoglobulin-like receptors (KIRs) and the CD94/NKG2A complex are critical inhibitory receptors found on Natural Killer (NK) cells and a subset of CD8+ T cells. These receptors function as immune checkpoints by binding to Human Leukocyte Antigen (HLA) class I molecules on target cells; KIRs generally recognize polymorphic HLA-A, -B, and -C ligands, while NKG2A binds to the non-classical HLA-E molecule (PMID: 30559448). This interaction triggers inhibitory signaling through immunoreceptor tyrosine-based inhibitory motifs (ITIMs), preventing NK cell activation against healthy tissues (UniProt P26715). In the context of oncology, tumors often overexpress HLA molecules to exploit these pathways and evade immune destruction. Therapeutic agents like monalizumab (anti-NKG2A) and lirilumab (anti-KIR) are designed to block these interactions, thereby restoring the cytotoxic potential of NK cells against malignant targets (PMID: 31105043). These therapies are currently being investigated, particularly in combination with other checkpoint inhibitors, to enhance anti-tumor immunity in both solid and hematological cancers (PMID: 25239233).

Other names

KIRCD94/NKG2AKiller cell inhibitory receptorsCD158KLRC1KLRD1/KLRC1 complexMHC class I-specific inhibitory receptors

Immune checkpoint inhibition by blocking inhibitory signals from HLA class I molecules, thereby restoring Natural Killer (NK) cell-mediated cytotoxicity against tumor cells.