Killer cell lectin-like receptor subfamily C member 1 (NKG2A) and Killer cell lectin-like receptor subfamily D member 1 (CD94) receptor complex (CD94/NKG2A)

The CD94/NKG2A receptor complex is a heterodimeric inhibitory receptor primarily expressed on natural killer (NK) cells and a subset of cytotoxic CD8+ T cells (Wikipedia, 2024; NIH, 2022). It belongs to the C-type lectin-like family and serves as a critical immune checkpoint by recognizing HLA-E, a non-classical MHC class I molecule (Frontiers in Immunology, 2022; NIH, 2008). HLA-E is frequently overexpressed in various malignancies, such as gastric adenocarcinoma and chronic lymphocytic leukemia, allowing tumor cells to evade immune surveillance by engaging the CD94/NKG2A complex and triggering inhibitory signals through its immunoreceptor tyrosine-based inhibitory motifs (ITIMs) (NIH, 2023; NIH, 2018). Therapeutic targeting of this complex, most notably with the monoclonal antibody monalizumab, aims to disrupt this inhibitory axis to unleash the anti-tumor potential of both innate and adaptive immune cells (NIH, 2023; NIH, 2022). Beyond oncology, the CD94/NKG2A complex is involved in regulating immune responses during chronic viral infections, such as HBV and HIV, and has been correlated with disease severity in COVID-19 patients (Frontiers in Immunology, 2022; Frontiers in Immunology, 2021).

Other names

KLRC1KLRD1CD159aKP43NKG2A/CD94CD94/NKG2A heterodimerKiller cell lectin-like receptor subfamily C member 1Killer cell lectin-like receptor subfamily D member 1

Monalizumab is a humanized IgG4 monoclonal antibody that blocks the interaction between the CD94/NKG2A receptor and its ligand HLA-E, thereby preventing the transmission of inhibitory signals to NK cells and CD8+ T cells and restoring their anti-tumor effector functions (NIH, 2023; NIH, 2022).