Killer cell lectin-like receptor subfamily C member 2 (NKG2C) – Antigen CD94 (CD94) receptor complex (CD94/NKG2C)

The CD94/NKG2C receptor complex is a heterodimeric activating receptor primarily expressed on natural killer (NK) cells and a subset of CD8+ T cells (UniProt P26717, Q13241). It is composed of the CD94 (KLRD1) and NKG2C (KLRC2) subunits, which together recognize the non-classical MHC class I molecule HLA-E (Wikipedia, 1.2.3). Unlike the inhibitory NKG2A/CD94 complex, NKG2C associates with the ITAM-containing adaptor protein DAP12 (TYROBP) to transmit activating signals that trigger cytotoxicity and the production of pro-inflammatory cytokines like IFN-gamma (1.2.1, 1.2.2). This complex is particularly significant in the context of human cytomegalovirus (HCMV) infection, where it drives the expansion of 'adaptive' NK cells with memory-like properties (1.1.1, 1.2.3). In therapeutic development, NKG2C is targeted to enhance anti-tumor immunity through agonistic antibodies, trispecific killer engagers (TriKEs), and engineered NK cell therapies (1.3.1, 1.3.2). The receptor is also being investigated for its role in glioblastoma and other cancers where HLA-E is overexpressed as an immune evasion mechanism (1.1.5). Conversely, its role in autoimmune diseases and transplant rejection suggests that modulating its activity could have broad clinical implications (1.2.3, 1.4.1). The balance between NKG2C and its inhibitory counterpart NKG2A is a critical factor in determining the overall immune response to tumors and chronic infections (1.4.3, 1.5.1).

Other names

KLRC2CD159cNKG2-CKLRD1CD94KP43Killer cell lectin-like receptor subfamily C member 2Antigen CD94CD159 Antigen-Like Family Member CNatural Killer Cell Receptor G2-C

Agonism of the activating receptor to stimulate natural killer cell-mediated lysis of target cells and the production of pro-inflammatory cytokines.