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

The Killer-cell immunoglobulin-like receptor (KIR)–Human leukocyte antigen (HLA) class I interaction axis is a critical immune checkpoint system that regulates the activity of natural killer (NK) cells and certain T cell subsets (PubMed: 29964471). Inhibitory KIRs recognize specific HLA class I molecules on the surface of healthy cells, delivering a signal that prevents NK cell-mediated lysis, a process essential for maintaining self-tolerance (UniProt: P43626). In many cancers, tumor cells continue to express HLA class I to evade NK cell surveillance by engaging these inhibitory receptors (PubMed: 28231465). Therapeutic strategies, such as the development of monoclonal antibodies like lirilumab, aim to block this interaction to "release the brakes" on NK cells, enabling them to identify and destroy malignant cells (ClinicalTrials.gov: NCT01687387). This axis is also significant in the context of hematopoietic stem cell transplantation, where KIR-HLA mismatch can lead to improved graft-versus-leukemia effects (PubMed: 15131251). Understanding the diversity of KIR and HLA genotypes is vital for predicting clinical responses to immunotherapies targeting this pathway.

Other names

KIR-HLA axisKIR-MHC class I interactionNK cell inhibitory checkpointKIR-HLA-C interaction

Antagonism of inhibitory KIR receptors to prevent their interaction with HLA class I ligands, thereby lowering the activation threshold for NK cells and enhancing their ability to kill tumor or infected cells (PubMed: 22406541).