Killer cell immunoglobulin-like receptor (KIR) and Major Histocompatibility Complex (MHC) class I interaction (KIR-MHC I interaction)

The interaction between Killer cell immunoglobulin-like receptors (KIRs) and Major Histocompatibility Complex (MHC) class I molecules (specifically HLA-A, -B, and -C) serves as a critical immune checkpoint that regulates the activity of Natural Killer (NK) cells and certain T cell subsets. Inhibitory KIRs recognize self-MHC class I molecules on healthy cells, delivering a signal that prevents NK cell activation and protects normal tissues from lysis. However, many tumors exploit this mechanism by maintaining MHC class I expression to evade immune surveillance, effectively 'turning off' NK cell responses. Therapeutic strategies targeting this interaction, such as monoclonal antibodies like lirilumab, aim to block these inhibitory signals. By preventing the binding of KIRs to their MHC ligands, these drugs lower the threshold for NK cell activation, thereby enhancing the immune system's ability to identify and destroy malignant or infected cells that would otherwise remain undetected.

Other names

KIR-HLA interactionKiller cell immunoglobulin-like receptor signalingNK cell inhibitory receptor axisMHC-I/KIR checkpoint

Blocking the interaction between inhibitory KIRs on NK cells and MHC class I (HLA) molecules on tumor cells to prevent inhibitory signaling and enhance NK cell-mediated anti-tumor cytotoxicity.