Natural killer cell receptors and ligands (NKRs/Ligands)

This target entry encompasses a broad system of Natural Killer (NK) cell regulatory molecules, primarily the Killer-cell Immunoglobulin-like Receptor (KIR) family and the NKG2D receptor, along with their respective Human Leukocyte Antigen (HLA) and stress-induced ligands (e.g., MICA/B). These molecules function as critical immunological checkpoints that balance NK cell activation and inhibition to maintain self-tolerance while identifying and eliminating stressed, infected, or malignant cells (Long EO, et al., 2013, Annu Rev Immunol; Lanier LL, 2015, Cancer Immunol Res). In the context of oncology, tumors frequently evade immune surveillance by upregulating inhibitory HLA ligands or by shedding activating stress ligands to downregulate NKG2D expression on NK cells and T cells (Lanier LL, 2015). Therapeutic interventions targeting this system include monoclonal antibodies like lirilumab and monalizumab, which block inhibitory signals to enhance NK cell-mediated tumor lysis, as well as emerging CAR-NK and bispecific engager technologies (ClinicalTrials.gov, 2024). Understanding the complex interplay between these diverse receptor-ligand pairs is essential for developing effective innate immune-based therapies for cancer and viral infections.

Other names

Killer-cell immunoglobulin-like receptorsNKG2DNatural cytotoxicity receptorsHLA class I ligandsStress-induced ligandsMICA/BULBPs

Modulation of NK cell activity through the blockade of inhibitory receptors (checkpoint inhibition) or the stimulation of activating receptors to enhance anti-tumor immunity.