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

NKG2A/CD94 is a heterodimeric inhibitory receptor complex primarily expressed on natural killer (NK) cells and a subset of cytotoxic T lymphocytes (CTLs) (Wikipedia, 2025; NIH, 2022). It belongs to the C-type lectin-like receptor family and specifically recognizes the non-classical MHC class I molecule, HLA-E, which presents peptides derived from the leader sequences of other HLA molecules (Wikipedia, 2025; NIH, 1998). This interaction serves as a critical "self-recognition" signal that prevents the immune system from attacking healthy cells (NIH, 2004; Wikipedia, 2025). However, many tumors overexpress HLA-E to evade immune surveillance by triggering the inhibitory signaling of NKG2A/CD94 (NIH, 2020; NIH, 2016). Therapeutic strategies, such as the monoclonal antibody monalizumab, aim to block this interaction to restore the anti-tumor activity of NK and T cells (Patsnap, 2024; Assay Genie, 2025).

Other names

CD159a/CD94KLRC1/KLRD1NKG2A-CD94 complexCD94/NKG2A inhibitory receptorCD159aKLRC1KLRD1CD94NKG2A

Monalizumab is a humanized monoclonal antibody that binds to the NKG2A receptor, preventing its interaction with the ligand HLA-E (NIH, 2020). This blockade inhibits the recruitment of SHP-1 phosphatase to the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of NKG2A, thereby restoring the cytotoxic activity and cytokine production of natural killer (NK) cells and CD8+ T cells against tumor cells (NIH, 2020; Patsnap, 2024).