Selection, tuning, and adaptation in mouse NK cell education

• Published in: Immunological reviews Vol. 267; no. 1; pp. 167 - 177
• Main Authors: Kadri, Nadir, Luu Thanh, Thuy, Höglund, Petter
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2015
• Subjects: Animals; education; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Ly49; Mice; Models, Immunological; NK cell; NK Cell Lectin-Like Receptor Subfamily A - immunology; NK Cell Lectin-Like Receptor Subfamily A - metabolism; Protein Binding - immunology; rheostat; selection; Self Tolerance - immunology; Signal Transduction - immunology; education; selection; rheostat; Ly49; NK cell
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12330

Summary Natural killer (NK) cells recognize transformed cells with an array of germline‐encoded inhibitory and activating receptors. Inhibitory Ly49 receptors bind major histocompatibility complex class I (MHC‐I) molecules, providing a mechanism by which NK cells maintain self‐tolerance yet eliminate cells expressing reduced levels of MHC‐I. Additionally, MHC‐I molecules are required for NK cell education, a process in which NK cells acquire responsiveness. In this review, we discuss three facets of MHC class I‐dependent education of mouse NK cells: skewing of the inhibitory receptor repertoire, induction of functional responsiveness, and tuning in response to changes in MHC‐I expression. We discuss prevailing models for education such as licensing and disarming and propose a model for positive selection of ‘useful’ NK cell subsets. Furthermore, we argue that both repertoire skewing and functional NK cell education may be altered in mature NK cells subject to changes in MHC‐I input and suggest that this process may provide increased dynamics to the NK cell system.