NKG2D ligand (stress-induced ligand) on target cell

"NKG2D ligands" (often called stress-induced ligands or "stress ligands" on target cells) are a family of MHC class I-related self-proteins that are minimally present on healthy cells but rapidly upregulated in response to cellular stress, transformation (as in cancer), DNA damage, infection, or senescence[2][3][4][5]. The human ligands in this group include MICA, MICB, and the UL16-binding proteins (ULBP1–ULBP6), all of which are recognized by the NKG2D activating receptor found on natural killer (NK) cells and some subsets of T cells[2][3][5]. Engagement of NKG2D by its ligands mediates cytotoxic responses that result in immune clearance of stressed or abnormal cells. These ligands are important in cancer immunosurveillance and antiviral defense; however, tumor cells may downregulate or shed these ligands to evade recognition, posing a major challenge to effective therapy[2][5]. Therapies harnessing or targeting this axis (e.g., NKG2D CAR-T or CAR-NK cells) are in development for cancer, but safety concerns such as off-tumor toxicity and immune evasion must be addressed[1][4]. Notes on "is_incorrect": The name "Stress ligands on target cells" is not a canonical target; it describes a category of molecules rather than a single specific entity or protein. The canonical specific targets are the individual NKG2D ligands (e.g., "Major histocompatibility complex class I polypeptide-related sequence A (MICA)", "UL16-binding protein 2 (ULBP2)"). The current entry is too broad and nonspecific to be mapped directly to a single molecular entity.

Other names

NKG2D ligandstress-induced ligandstress ligandMICAMICBULBP1-6major histocompatibility complex class I chain-related protein A/BUL16-binding proteins

Engagement of NKG2D ligands triggers activation of NKG2D receptor on NK cells and some T cells, leading to lysis of the ligand-expressing (stressed) target cell[2][3][5].