Natural Killer and invariant Natural Killer T cell-recognized ligands (NK/iNKT ligands)

This target refers to a diverse group of cell-surface molecules upregulated by cells undergoing oncogenic transformation, viral infection, or physiological stress, which serve as 'eat-me' signals for the innate immune system. Key components include NKG2D ligands (such as MICA, MICB, and ULBPs) and CD1d, which presents lipid antigens to invariant Natural Killer T (iNKT) cells (PMID: 11491520, 17291282). These ligands are typically absent or expressed at low levels on healthy resting cells but are highly induced by DNA damage, oxidative stress, or heat shock, acting as markers of cellular distress (PMID: 11777960). Therapeutic strategies targeting this axis include CAR-T or CAR-NK cells engineered with NKG2D receptors, bispecific antibodies, and CD1d agonists like alpha-galactosylceramide designed to enhance the recognition and elimination of cancer cells (PMID: 28807980). However, a significant challenge is the proteolytic shedding of ligands like MICA/B by tumor cells, which creates soluble decoys that inhibit immune cell function and facilitate tumor escape (PMID: 12446910).

Other names

NKG2D ligandsCD1d-presented antigensStress-induced ligandsNK cell activating ligands

Activation of Natural Killer (NK) and invariant Natural Killer T (iNKT) cells through the engagement of activating receptors (e.g., NKG2D) or the TCR-CD1d complex, leading to targeted cytotoxicity and cytokine release against malignant or stressed cells.