Natural killer cell surface antigens (NK cell antigens)

Natural killer (NK) cell surface antigens are a heterogeneous group of proteins, including receptors and glycoproteins, that dictate the functional state of NK cells within the innate immune system (Vivier et al., 2011, Science). These antigens are broadly categorized into activating receptors, such as NKG2D and the Natural Cytotoxicity Receptors (NKp30, NKp44, NKp46), and inhibitory receptors, most notably the Killer-cell Immunoglobulin-like Receptors (KIRs) and the CD94/NKG2A complex (Lanier, 2005, Annu Rev Immunol). Activating receptors recognize stress-induced ligands on malignant or infected cells, while inhibitory receptors recognize self-MHC class I molecules to prevent the destruction of healthy tissue (Long et al., 2013, Annu Rev Immunol). CD16 (FcγRIIIa) is another pivotal surface antigen that enables NK cells to execute antibody-dependent cellular cytotoxicity (ADCC) by binding to the Fc region of IgG antibodies (Wang et al., 2015, Front Immunol). In oncology, these antigens are therapeutic targets for monoclonal antibodies like Monalizumab (targeting NKG2A) and Lirilumab (targeting KIRs), which aim to release the brakes on NK cell activity (Andre et al., 2018, Cell). Additionally, bispecific and trispecific NK cell engagers (NKCEs) are being developed to bridge NK cell activating receptors directly to tumor-associated antigens, enhancing targeted cell lysis (Gauthier et al., 2019, Cell).

Other names

NK cell markersNatural killer cell receptorsNK cell surface proteinsNK cell cluster of differentiation antigens

Modulation of NK cell activity through the blockade of inhibitory receptors (checkpoint inhibition) or the stimulation of activating receptors to induce tumor cell lysis and cytokine release.