Killer cell immunoglobulin-like receptor 3DL1 – Human leukocyte antigen Bw4 allotypes (KIR3DL1–HLA-Bw4)

The KIR3DL1 – HLA-Bw4 allotypes target refers to the interaction between the inhibitory Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) and its cognate ligands, the Human Leukocyte Antigen (HLA) Bw4 allotypes [1, 16]. KIR3DL1 is primarily expressed on natural killer (NK) cells and a subset of T cells, where it plays a critical role in immune surveillance and "missing-self" recognition [3, 10]. Upon binding to HLA-Bw4 molecules on healthy cells, KIR3DL1 transmits inhibitory signals that prevent NK cell-mediated lysis, thereby maintaining self-tolerance [16, 23]. However, many cancer cells and virus-infected cells exploit this mechanism by maintaining or upregulating HLA-Bw4 expression to evade immune detection [1, 6]. Therapeutic strategies targeting this interaction involve the use of checkpoint inhibitors, such as monoclonal antibodies, to block the inhibitory signal and reactivate NK cells against the diseased cells [2, 21]. The efficacy of these treatments is highly dependent on the specific allotypes of both the receptor and the ligand, as polymorphisms in KIR3DL1 (high, low, or null expression) and HLA-Bw4 (80I or 80T subtypes) significantly influence binding affinity and NK cell education [4, 13, 14]. Clinical interest in this target spans oncology, particularly in hematologic malignancies like leukemia and lymphoma, as well as infectious diseases such as HIV and COVID-19 [5, 9, 11].

Other names

CD158e1KIR3DL1NKB1NKAT3HLA-Bw4MHC class I Bw4Bw4-80IBw4-80TKIR3DL1-HLA-Bw4 interaction

Checkpoint inhibition and NK cell activation by blocking the inhibitory interaction between KIR3DL1 and HLA-Bw4.