Figure 1. Innate immunity recognizes changes in cells induced by infection.

NK cells have inhibitory receptors on their surface to differentiate “self” from “missing-self”. The lack of expression of MHC class I molecules (missing self) promotes the activation of NK cells and subsequent lysis of the target cells. NK cells also express activating receptors such as NKG2D that directly recognize ligands induced in response to infection (induced self). NK cell-mediated cytotoxicity against malignant target cells or infected cells is regulated by both activating and inhibitory cell surface immunoreceptors. In humans, such receptors are of three types: 1) the killer immunoglobulin receptors (KIRs), 2) natural cytotoxicity receptors (NCRs), and 3) the c-type lectin receptors. NKG2D is one member of the c-type lectin-activating receptor family that is evolutionarily conserved and is located within the NK gene complex on human chromosome 12p12-p13. NKG2D is expressed on all NK cells and is a promiscuous receptor that recognizes at least 6 counter ligands that include: the MHC class I-like molecules, MICA and MICB, and members of the ULBP family (ULPB1-4), named for the ability of some members to bind to the UL-16 protein of cytomegalovirus (CMV).