CD94-NKG2A receptor (NKG2A/CD94)

The CD94-NKG2A receptor is a dimeric surface receptor composed of CD94 and NKG2A subunits, belonging to the C-type lectin family. It is expressed on NK cells and a subset of cytotoxic T lymphocytes. The complex binds to non-classical MHC class I molecules, specifically HLA-E in humans and Qa-1^b^ in mice, which present peptides derived from cellular signal sequences. Upon ligand binding, the cytoplasmic domain of NKG2A transmits an inhibitory signal via immunoreceptor tyrosine-based inhibitory motifs (ITIMs), restraining the cytotoxic activity of NK and T cells. The receptor regulates immune responses by discriminating "self" from "altered self," preventing the killing of healthy cells while allowing immune surveillance and cytotoxicity against cells lacking proper MHC class I expression, such as tumor or infected cells. Checkpoint blockade therapies, like monoclonal antibodies that inhibit NKG2A, are investigated in oncology and infectious diseases to potentiate antitumor and antiviral immune responses. Because the complex is a key immune modulator, its targeting is associated with safety concerns typical of immune checkpoint therapies, including potential exacerbation of autoimmunity and excessive immune activation.

Other names

CD94-NKG2A complexNKG2A-CD94 heterodimerKLRC1-CD94 complexNK cell inhibitory receptorCD94-NKG2A

Drugs such as anti-NKG2A monoclonal antibodies block the inhibitory signal, enhancing NK and cytotoxic T cell activity against tumor or infected cells. By inhibiting NKG2A/CD94, checkpoint blockade releases inhibition and boosts immune cell cytotoxicity.