Figure 8.

Mechanisms of target cell recognition by natural killer (NK) cells. NK cells lack clonotypic receptors and rely on germline-encoded activation and inhibitory receptors to recognize other cells around them. The following are some of the primary mechanisms by which NK cells perceive target cells. (A) “Immunological Self”: recognition of autologous MHC class I (MHC-I) (human leukocyte antigen (HLA)) or histocompatibility antigen-2 (H2, mouse) by inhibitory receptors [killer cell immunoglobulin-like receptor (KIR) or Ly49] let the NK cells know that they are interacting with normal cells and contain their activation. (B) “Missing-self”: recognition of target cells that either does not express MHC-I or reduce them below optimal levels can induce NK cell activation. (C) “Induced-self”: recognition of activating ligands that are expressed on target cells by the germline-encoded receptors such as NKG2D (H60, mouse; MIC-A/B, human), Ly49H (murine cytomegalovirus-derived m157, mouse), NCR1 (a number of viral proteins) can overcome MHC-I-mediated inhibitory signaling resulting in NK cell activation. (D) “Non-self”: recognition of transplanted tissue by NK cells, where the donor tissue expresses either allogeneic or haploidentical MHC-I.