Killer cell lectin-like receptor subfamily D member 1 (CD94) (CD94)

Killer cell lectin-like receptor subfamily D member 1 (CD94) is a type II transmembrane protein that plays a critical role in modulating the activity of natural killer (NK) cells and a subset of cytotoxic CD8+ T cells [1, 2]. It functions by forming disulfide-linked heterodimers with members of the NKG2 family, most notably the inhibitory NKG2A or the activating NKG2C, to recognize the non-classical MHC class I molecule HLA-E [1, 3]. In malignant contexts, such as extranodal NK/T-cell lymphoma and various solid tumors, the CD94/NKG2A complex is frequently exploited by cancer cells to evade immune surveillance through the overexpression of HLA-E [4, 5]. When CD94/NKG2A binds to HLA-E, it triggers inhibitory signaling via ITIM motifs in the NKG2A tail, suppressing the immune cell's ability to kill the target cell [3, 6]. Therapeutic strategies, such as the monoclonal antibody monalizumab, target this pathway by blocking the CD94/NKG2A-HLA-E interaction, thereby 'unleashing' the anti-tumor effector functions of both NK and T cells [7, 8]. This makes CD94 a significant target in the field of next-generation immune checkpoint therapy, particularly for patients whose tumors exhibit high HLA-E expression [5, 9]. [1] UniProt (Q13241); [2] NCBI Gene (KLRD1); [3] Vance et al., Journal of Experimental Medicine (1999); [4] Kamiya et al., Blood (2019); [5] André et al., Cell (2018); [6] Borst et al., Nature Reviews Immunology (2020); [7] ClinicalTrials.gov (NCT02671435); [8] van Hall et al., Cell (2019); [9] McWilliams et al., Journal for ImmunoTherapy of Cancer (2022).

Other names

KLRD1KP43Killer cell lectin-like receptor D1CD94 antigenNatural killer cell receptor CD94

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