Fig. 2

Mechanisms of target recognition by NK cells and subsequent activation. Their activation is tightly regulated and involves a complex interplay of activating and inhibitory signals. “Normal circumstance”: NK cells recognize autologous MHC class I molecules through inhibitory receptors like killer cell immunoglobulin-like receptor (KIR), indicating the interaction with normal cells and suppressing their activation. “Missing-self”: NK cells recognize target cells that either lack expression or have reduced levels of MHC class I molecules, such as infected or transformed cells. This recognition leads to the activation of NK cells. “Stress-induced”: NK cells recognize activating ligands expressed on target cells through NK receptors like NKG2D. This recognition can override MHC class I-mediated inhibitory signaling, resulting in the activation of NK cells. “Non-self”: NK cells recognize transplanted tissue when the donor tissue expresses either allogeneic or haploidentical MHC class I molecules. Figure created using BioRender (Created with biorender.com/)