Natural killer cell education in human health and disease

• Published in: Current opinion in immunology 2018-02, Vol.50, p.102-111
• Main Authors: Boudreau, Jeanette E, Hsu, Katharine C
• Format: Article
• Language: English
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2017.11.003

•NK cell education is endowed by independently-segregating polygenic KIR and HLA which, combined, enable diverse effector functions.•Education counterbalances each NK cell's effector potential with sensitivity for inhibition.•Uneducated and educated NK cells have roles in successful pregnancy, disease resistance and susceptibility. Natural killer (NK) cells maintain immune homeostasis by detecting and eliminating damaged cells. Simultaneous activating and inhibitory input are integrated by NK cells, with the net signal prompting cytotoxicity and cytokine production, or inhibition. Chief among the inhibitory ligands for NK cells are ‘self’ human leukocyte antigen (HLA) molecules, which are sensed by killer immunoglobulin-like receptors (KIR). Through a process called ‘education’, the functional capabilities of each NK cell are counterbalanced by their sensitivity for inhibition by co-inherited ‘self’ HLA. HLA and their ligands, the killer immunoglobulin-like receptors (KIR), are encoded by polymorphic, polygenic gene loci that segregate independently, therefore, NK education and function differ even between related individuals. In this review, we describe how variation in NK education, reactivity and sensitivity for inhibition impacts reproductive success, infection, cancer, inflammatory and autoimmune diseases.