Major histocompatibility complex class I polypeptide-related sequence A (MICA) and B (MICB) (MICA; MICB)

NKG2D ligands, principally MICA and MICB in humans, are cell-surface glycoproteins induced by cellular stress such as oncogenic transformation, DNA damage, or infection. They serve as activating signals for cytotoxic lymphocytes—especially NK cells and some T cell subsets—through the NKG2D receptor, enabling immune surveillance and elimination of transformed or infected cells. Tumors often evade this immune detection by shedding or downregulating these ligands, leading to immune escape. Targeting this pathway holds promise in cancer immunotherapy, particularly with engineered immune cells that exploit NKG2D ligand recognition to target malignant cells.

Other names

NKG2D ligandstress-induced ligandMICULBP family (ULBP1–6)NKG2DL

Promotes immune-mediated cytotoxicity via NKG2D receptor activation; involved in immune escape via shedding/cleavage from tumor cell surface.