They also mediate host injury by exerting cytotoxicity that is facilitated by natural killer cell-activating receptors, such as NKG2D, and cytolytic molecules, such as granzyme B. Interestingly, it has been recently reported that there is a strong association between the cytolytic function of bystander-activated CD8<sup>+</sup> T cells and host tissue injury in patients with acute hepatitis A virus infection.
NKG2D recognizes various MHC I-like ligands that are induced on target cells exposed to stressors such as viral infection, DNA damage and oncological transformation.
We now report that increased expression of NKG2D ligands after virus infection depends on interferon response factors activated by the detection of viral double-stranded RNA by pattern-recognition receptors (RIG-I/MDA-5) and that NKG2D ligand up-regulation can be blocked by the expression of viral dsRNA-binding proteins.
NKG2D is an activating receptor that can bind to a large number of stress-induced ligands that are expressed in the context of cancer or viral infection.
The recognition of ectopic surface-expressing endogenous antigen by TCRγδ and NKG2D may be an important mechanism of innate immune response to carcinogenesis and viral infection.
Taken together, our data suggest that ULBP4 functions as a ligand for both TCRgammadelta and NKG2D and may play a key role in immune surveillance of tumor development and clearance of viral infection.