NKG2D

Protein KLRK1 PDB 1hyr

NKG2D

NKG2D, also known as natural killer group 2D, is a type II transmembrane receptor protein that plays a crucial role in the immune system. It is encoded by the NKG2D gene located on human chromosome 12. NKG2D is primarily expressed on the surface of natural killer (NK) cells, CD8+ T cells, and some γδ T cells.

Structure

NKG2D is a homodimeric receptor composed of two subunits, each containing a C-type lectin-like domain. The ligands for NKG2D are stress-induced proteins that are upregulated in response to cellular stress, infection, or transformation. Upon ligand binding, NKG2D triggers signaling cascades that lead to the activation of immune cells and the elimination of target cells.

Function

The main function of NKG2D is to recognize and eliminate cells that display signs of stress or abnormality, such as infected cells or cancer cells. NKG2D ligands include major histocompatibility complex class I-related chain A (MICA), MHC class I chain-related protein A (MICB), and UL16-binding proteins (ULBPs). Engagement of NKG2D with its ligands results in the activation of cytotoxic mechanisms in NK cells and CD8+ T cells, leading to the destruction of target cells.

Regulation

The expression of NKG2D ligands is tightly regulated to prevent inappropriate activation of the immune system. Various mechanisms, such as proteolytic shedding and endocytosis, control the surface expression of NKG2D ligands. Dysregulation of NKG2D signaling has been implicated in autoimmune diseases, chronic infections, and cancer immune evasion.

Clinical Significance

Aberrant NKG2D signaling has been associated with various diseases, including autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus, as well as cancer progression and immune escape. Targeting the NKG2D pathway has emerged as a potential therapeutic strategy for enhancing immune responses against cancer cells and infected cells.

See Also

• Natural Killer Cell
• T Cell Receptor
• Immune System