Killer-cell immunoglobulin-like receptor–Human leukocyte antigen class I axis (KIR–HLA-I axis) (KIR–HLA-I axis)

The Killer-cell immunoglobulin-like receptor (KIR)–Human leukocyte antigen (HLA) class I axis is a pivotal immune checkpoint system that regulates the effector functions of natural killer (NK) cells and certain T cell subsets (Source: Sivori et al., 2019, Frontiers in Immunology). Under physiological conditions, inhibitory KIRs on NK cells bind to HLA class I molecules (specifically HLA-C, HLA-Bw4, and HLA-A3/11) on healthy cells to prevent autologous attack and maintain self-tolerance (Source: Pende et al., 2019, Blood). In the context of oncology, many tumor cells exploit this mechanism by maintaining HLA expression to deliver inhibitory signals that allow them to evade NK cell-mediated surveillance (Source: Carlsten and Malmberg, 2015, Frontiers in Immunology). Therapeutic strategies targeting this axis, such as the monoclonal antibody lirilumab, work by blocking the interaction between inhibitory KIRs (like KIR2DL1/2/3) and their HLA ligands, thereby lowering the activation threshold for NK cells to attack the tumor (Source: Vey et al., 2012, Blood). While monotherapy has shown limited clinical success, the axis remains a significant target for combination therapies aimed at enhancing the innate immune response against both hematological and solid malignancies (Source: He et al., 2022, Journal of Hematology & Oncology).

Other names

KIR-MHC class I axisNK cell immune checkpointKIR-HLA interactionKiller-cell immunoglobulin-like receptor-MHC class I interaction

Monoclonal antibodies block inhibitory KIR receptors (e.g., KIR2DL1/2/3) from binding to HLA class I ligands, preventing the transmission of inhibitory signals and enhancing NK cell-mediated lysis of target cells.