Natural killer cell receptors on natural killer T cells (NKRs on NKT cells)

Natural killer (NK) receptors on natural killer T (NKT) cells are a heterogeneous group of surface proteins that modulate the activation, exhaustion, and effector functions of NKT cells. NKT cells are a specialized subset of T lymphocytes that express both a T-cell receptor (TCR) and various receptors typically associated with NK cells, such as NKG2D, KIRs, and CD94/NKG2 complexes (Vivier et al., 2004, Nature Reviews Immunology). These endogenous receptors allow NKT cells to respond to stress-induced ligands and MHC-class-I-like molecules, providing a rapid innate-like response to tumors and pathogens (Godfrey et al., 2004, Nature Reviews Immunology). In therapeutic applications, these receptors are targeted to enhance the anti-tumor efficacy of NKT cells, either through the use of monoclonal antibodies that block inhibitory signals like NKG2A or through bispecific engagers that trigger activating receptors (André et al., 2018, Cell). Because NKT cells can bridge the innate and adaptive immune systems, modulating their endogenous NK receptors offers a potent pathway for treating various cancers and infectious diseases (Van Kaer, 2005, Nature Reviews Immunology). However, therapeutic manipulation of these receptors requires careful management to avoid systemic cytokine release syndrome or autoimmune reactions (Smyth et al., 2002, Nature Reviews Immunology).

Other names

NK receptorsNKT cell receptorsEndogenous NKRsNatural killer receptorsActivating and inhibitory NK receptors

Modulation of NKT cell activity through the blockade of inhibitory receptors (checkpoint inhibition) or the stimulation of activating receptors to enhance anti-tumor cytotoxicity and cytokine release.