NK-cell activating ligands and altered self markers

NK-cell activating ligands and altered self markers represent a heterogeneous group of cell surface molecules that signal cellular distress, transformation, or infection to Natural Killer (NK) cells. Activating ligands, such as MHC class I polypeptide-related sequence A and B (MICA/B) and UL16-binding proteins (ULBPs), are typically upregulated in response to DNA damage or oncogenic transformation and bind to activating receptors like NKG2D (Vivier et al., 2011). Conversely, altered self refers to the loss or downregulation of classical MHC class I molecules, a phenomenon known as missing-self recognition, which removes inhibitory signals and triggers NK cell activation (Ljunggren & Kärre, 1990). Tumor cells often exploit these pathways by shedding activating ligands as soluble decoys or upregulating inhibitory markers like HLA-E to evade immune surveillance (André et al., 2018). Therapeutic strategies targeting these markers include monoclonal antibodies that block inhibitory checkpoints, bispecific NK-cell engagers, and CAR-NK cell therapies designed to restore or amplify the immune system's ability to detect these cellular abnormalities. Understanding the balance between these activating and inhibitory signals is crucial for developing effective immunotherapies against various cancers and viral infections.

Other names

Stress-induced ligandsNKG2D ligandsMissing-self markersMHC class I-related chainsNK cell activating ligands

Enhancement of NK cell-mediated tumor cell lysis by engaging activating receptors or blocking inhibitory checkpoint interactions between tumor ligands and NK cell receptors.