Natural killer group 2D (NkG2D) is a vital activating receptor expressed on NK cells, CD8+ T cells, γδT cells, and NKT cells. It directly binds stress-induced ligands (e.g., MICA, MICB, ULBPs) overexpressed on tumor or infected cells, triggering cytotoxic immune responses via perforin/granzyme release without requiring antigen presentation. This ligand-receptor interaction facilitates tumor immune surveillance and drives adaptive immunity, positioning NkG2D as a critical target in cancer immunotherapy. Its ligands, rarely expressed in healthy tissues, are upregulated during malignant transformation, viral infection, or cellular stress, enabling precise targeting of diseased cells. Research applications span cancer immunotherapies (e.g., CAR-T/NK cell engineering), autoimmune disease modulation, and studies on inflammatory disorders like atherosclerosis. NkG2D-based strategies hold broad therapeutic potential due to their dual role in innate and adaptive immunity.
Fig.1 NkG2D receptor and its ligand.1
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