Killer cell lectin-like receptor subfamily C member 1 (NKG2A) (NKG2A)

NKG2A (Killer cell lectin-like receptor subfamily C member 1) is a prominent inhibitory checkpoint receptor primarily expressed on the surface of Natural Killer (NK) cells and a subset of cytotoxic CD8+ T lymphocytes (UniProt P26715). It functions as a heterodimer with CD94 to recognize HLA-E, a non-classical MHC class I molecule that is frequently overexpressed in various cancers to facilitate immune evasion (PubMed: 30503213). Upon binding to HLA-E, NKG2A transmits inhibitory signals through its immunoreceptor tyrosine-based inhibitory motifs (ITIMs), effectively dampening the cytotoxic response of the immune system against tumor cells. Therapeutic strategies targeting NKG2A, such as the monoclonal antibody monalizumab, aim to block this inhibitory axis, thereby "releasing the brakes" on both innate and adaptive immunity. This approach is particularly promising when used in combination with other checkpoint inhibitors, such as those targeting the PD-1/PD-L1 pathway, to enhance anti-tumor efficacy in solid and hematological malignancies (ClinicalTrials.gov: NCT02643550).

Other names

CD159aKLRC1NKG2ANK cell receptor ACD94/NKG2A complex

Immune checkpoint inhibition by blocking the interaction between the NKG2A/CD94 heterodimer and its ligand HLA-E, thereby restoring the cytotoxic activity of NK cells and CD8+ T cells.