NKG2D

NKG2D is an activating receptor found on NK cells and CD8 T cells (both αβ and γδ) which was first identified in 1991 and is encoded by the KLRK1 gene. Its function as an activating receptor was first described in 1999, and its ligands are stress-induced proteins such as MICA, is_associated_with::MICB, is_associated_with::ULBP1, is_associated_with::ULBP2, is_associated_with::ULBP3, and ULBP4-6 for human NKG2D, and Rae-1, Mult1, and H-60 for murine NKG2D.

Structure
The structure of NKG2D consists of two disulphide-linked type II transmembrane proteins with short intracellular domains incapable of transducing signals. They therefore require adaptor proteins in order to transduce signals, and this receptor uses two adapter proteins, is_associated_with::DAP10 and is_associated_with::DAP12, which associate as homodimers to the receptor - therefore the entire receptor complex appears as a hexamer.

Function
The ligands for NKG2D are induced during times of cellular stress, either as a result of is_associated_with::infection or genomic stress such as in is_associated_with::cancer, which renders the cell susceptible to NK cell mediated lysis. The function of NKG2D on CD8 T cells is to send co-stimulatory signals to activate them.

Role in viral infection
Viruses, as intracellular pathogens, can induce the expression of stress ligands for NKG2D. NKG2D is thought to be important in viral control as viruses have adapted mechanisms by which to evade NKG2D responses. For example, is_associated_with::cytomegalovirus (CMV) encodes a protein, is_associated_with::UL16, which binds to NKG2D ligands ULBP1 and 2 (thus their name "UL16-binding protein") and MICB, which prevents their surface expression.

Role in tumour control
As cancerous cells are "stressed", NKG2D ligands become upregulated, rendering the cell susceptible to NK cell-mediated lysis. Tumor cells that can evade NKG2D responses are thus more likely to propagate.