Natural killer cell lectin-like receptor subfamily C member 1 – HLA class I histocompatibility antigen, alpha chain E interaction (NKG2A – HLA-E interaction)

The NKG2A – HLA-E interaction is a critical inhibitory immune checkpoint axis that regulates the activity of natural killer (NK) cells and a subset of cytotoxic CD8+ T cells. NKG2A (encoded by KLRC1) forms a heterodimer with CD94 to recognize HLA-E, a non-classical MHC class I molecule that presents peptides derived from the leader sequences of other MHC class I molecules. In many cancers, HLA-E is overexpressed as a mechanism of immune evasion, effectively 'switching off' the immune response by binding to NKG2A on infiltrating lymphocytes. Therapeutic strategies, most notably the monoclonal antibody monalizumab, aim to block this interaction to enhance the anti-tumor surveillance and effector functions of the innate and adaptive immune systems. This target is particularly significant in the context of combination therapies with PD-1/PD-L1 inhibitors, as it addresses a distinct pathway of resistance in the tumor microenvironment.

Other names

NKG2A – HLA-E axisCD159a – HLA-E interactionKLRC1 – HLA-E interactionCD94/NKG2A – HLA-E complex

Immune checkpoint inhibition by blocking the binding of the inhibitory receptor NKG2A to its ligand HLA-E, thereby restoring the cytotoxic activity of natural killer (NK) cells and CD8+ T cells against tumor cells.