Abnormal host cells recognized by NK cells via stress ligands and altered MHC class I

Abnormal host cells recognized by NK cells via stress ligands and altered MHC class I refers to a cellular state, typically found in malignant or virally infected cells, that renders them susceptible to Natural Killer (NK) cell-mediated destruction. This recognition is governed by a balance of signals: the 'missing-self' mechanism occurs when cells downregulate MHC class I to evade T-cells, which removes inhibitory signals to NK cell Killer-cell Immunoglobulin-like Receptors (KIRs) (Ljunggren & Kärre, 1990, Immunology Today). Concurrently, 'induced-self' recognition involves the upregulation of stress-induced ligands (such as MICA, MICB, and ULBPs) that bind to the activating receptor NKG2D on NK cells (Lanier, 2015, Nature Reviews Immunology). In therapeutic contexts, this axis is targeted by checkpoint inhibitors like Lirilumab (anti-KIR) and Monalizumab (anti-NKG2A) to disinhibit NK cells, or by CAR-NK cells and bispecific engagers that specifically bind to stress ligands on the abnormal cells (Vivier et al., 2011, Science; André et al., 2018, Cell). This target description represents a physiological mechanism of immune evasion and recognition rather than a single molecular entity.

Other names

MHC-I deficient cellsStressed host cellsNKG2D ligand-expressing cellsMissing-self targetsInduced-self targets

Enhancement of NK cell-mediated cytotoxicity by blocking inhibitory receptors (e.g., KIR, NKG2A) or activating NK cells through stress-ligand recognition (e.g., NKG2D engagement).