Killer cell lectin-like receptor subfamily D member 1 (KLRD1)

Killer cell lectin-like receptor subfamily D member 1 (KLRD1), also known as CD94, is a type II transmembrane receptor and member of the C-type lectin superfamily predominantly expressed on the surface of natural killer (NK) cells and subsets of cytotoxic T cells[1][2]. KLRD1 forms disulfide-bonded heterodimers with members of the NKG2 family, most notably NKG2A and NKG2C, to recognize the non-classical MHC class I molecule HLA-E on target cells. These heterodimers play a central role in regulating NK cell activity by providing inhibitory or activating signals, thus maintaining self-tolerance and modulating cytotoxic responses[2][4][5]. By monitoring the expression of HLA-E, the KLRD1-containing complexes serve as immune checkpoints, contributing both to surveillance against tumors and pathogens and to mechanisms of immune evasion and exhaustion in cancer[2][5]. KLRD1 is considered a therapeutic target in immuno-oncology, and blockade of its associated inhibitory pathways (such as with anti-NKG2A antibodies) is under clinical investigation to restore anti-tumor immunity[2][3][5].

Other names

CD94NK cell receptorKP43Natural killer cells antigen CD94Killer cell lectin-like receptor D, member 1

Immune checkpoint inhibition (blocking the CD94/NKG2A–HLA-E interaction to enhance NK and T cell cytotoxicity against tumor or infected cells)[2]