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

Killer immunoglobulin-like receptors (KIRs) are a diverse family of cell surface proteins found primarily on Natural Killer (NK) cells and a subset of T cells, where they regulate immune activity through interactions with Human Leukocyte Antigen (HLA) class I molecules (Source: UniProt, P43626). These receptors can be either inhibitory or activating; inhibitory KIRs recognize specific HLA-A, -B, or -C alleles on healthy cells to maintain self-tolerance and prevent autoimmune damage (Source: NIH, PMC3741539). In many cancers, tumor cells downregulate HLA expression to evade T-cell detection, but this "missing self" signal can be recognized by NK cells when inhibitory KIR signals are absent, leading to tumor lysis (Source: PubMed, 21849449). Therapeutic strategies, such as the monoclonal antibody Lirilumab, aim to block inhibitory KIRs to prevent them from binding to HLA ligands, thereby lowering the activation threshold for NK cells to attack malignant cells (Source: ClinicalTrials.gov, NCT01687387). The KIR-HLA system is also a critical factor in the success of hematopoietic stem cell transplantation, where KIR-ligand mismatching can promote a beneficial graft-versus-leukemia effect (Source: Nature Reviews Immunology, 2008). Additionally, specific KIR-HLA combinations are linked to the progression of viral infections like HIV and various autoimmune conditions (Source: PubMed, 15549153).

Other names

KIR-MHC class I interactionCD158Killer cell immunoglobulin-like receptorsKIR-HLA interaction

Checkpoint inhibition by blocking inhibitory KIR receptors to prevent their interaction with HLA class I ligands, thereby enhancing natural killer (NK) cell-mediated anti-tumor immunity.