Natural killer cell receptor subunit NKG2A (NKG2A)

Natural killer cell receptor subunit NKG2A is a type II transmembrane glycoprotein that forms a heterodimer with CD94 on the surface of most human natural killer (NK) cells and some cytotoxic T lymphocytes. This complex functions as an inhibitory immune checkpoint by recognizing non-classical MHC class I molecules—specifically HLA-E in humans—presenting peptides derived from other MHC class I leader sequences. Upon ligand engagement, the intracellular ITIM domains recruit phosphatases that suppress activation signals, thereby inhibiting cytotoxicity and cytokine production. This mechanism prevents inappropriate killing of healthy “self” cells but can be exploited by tumors or infected cells expressing high levels of HLA-E to evade immune surveillance. Therapeutic blockade with monoclonal antibodies such as monalizumab aims to restore anti-tumor immunity by releasing this brake on effector lymphocytes[4][5][6].

Other names

Killer cell lectin-like receptor subfamily C member 1KLRC1CD159aNKG2-ACD94/NKG2A (when referring to the functional heterodimer)NK cell inhibitory receptor NKG2A

Blockade of the inhibitory signal delivered by NKG2A/CD94 upon binding to HLA-E on target cells enhances cytotoxic activity of NK and CD8+ T cells[4][5][6]