NKG2D is a type II transmembrane glycoprotein having an extracellular lectin-like domain. This domain lacks the recognizable calcium-binding sites found in true C-type lectins and binds protein rather than carbohydrate ligands. Human ligands for NKG2D include MICA, MICB, and ULBP1, 2, and 3. Expression of NKG2D ligands occurs in epithelial cells, tumor cells and under conditions of stress or infection. NKG2D exists as a disulfide-linked homodimer that delivers an activating signal upon ligand binding. Signaling requires association with an adapter protein. Alternative splicing of the NKG2D mRNA results in isoforms with different cytoplasmic domains that can associate either with DAP12 to deliver a true activating signal or with DAP10 resulting in a costimulatory signal. NKG2D has been implicated in anti-tumor surveillance and the immune response against viral infection. In NK cells, NKG2D serves as an activating receptor, which itself is able to trigger cytotoxicity. The function of NKG2D on CD8+ T cells is to send co-stimulatory signals to activate them.