Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned

• Published in: Trends in immunology Vol. 39; no. 3; pp. 222 - 239
• Main Authors: Boudreau, Jeanette E., Hsu, Katharine C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2018; Elsevier Limited
• Subjects: Animal models; Animals; Antigens; Cancer; Cancer therapies; Cell Differentiation; Cytotoxicity, Immunologic; Education; Epigenesis, Genetic; Genetic diversity; Genetic Predisposition to Disease; Haplotypes; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Humans; Immune System Diseases - genetics; Immune System Diseases - immunology; Immunoglobulins; Immunotherapy; Killer cell immunoglobulin-like receptors; Killer Cells, Natural - physiology; Leukemia; Licenses; Ligands; Ly-49 antigen; Lymphocyte Activation; Major histocompatibility complex; Mice; Natural killer cells; Neoplasms - genetics; Neoplasms - immunology; Neuroblastoma; Phosphatase; Polymorphism, Genetic; Receptors, KIR - genetics; Receptors, KIR - metabolism; Signal Transduction; Transplants & implants
• ISSN: 1471-4906; 1471-4981; 1471-4981
• DOI: 10.1016/j.it.2017.12.001

The functional capacities of natural killer (NK) cells differ within and between individuals, reflecting considerable genetic variation. ‘Licensing/arming’, ‘disarming’, and ‘tuning’ are models that have been proposed to explain how interactions between MHC class I molecules and their cognate inhibitory receptors – Ly49 in mice and KIR in humans – ‘educate’ NK cells for variable reactivity and sensitivity to inhibition. In this review we discuss recent progress toward understanding the genetic, epigenetic, and molecular features that titrate NK effector function and inhibition, and the impact of variable NK cell education on human health and disease. NK cell function is calibrated through a process called ‘education’. The reactive potential of each NK cell is counterbalanced by its sensitivity to inhibition by self-MHC class I molecules. Immunogenetic variability confers different education programs between individual subjects, leading to variable sensitivity to activating and inhibitory input. Differences in NK cell education, which can be predicted by NK immunogenetics, impact susceptibility and resistance to specific disease phenotypes.