Selection, tuning, and adaptation in mouse NK cell education.
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.
Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Nadir
N
Kadri
Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Thuy Luu
TL
Thanh
Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.|Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Petter
P
Höglund
D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A
Ly49; NK cell; education; rheostat; selection