title: Know Thyself: NK-Cell Inhibitory Receptors Prompt Self-Tolerance, Education, and Viral Control.
abstract: Natural killer (NK) cells provide essential protection against viral infections. One of the defining features of this lymphocyte population is the expression of a wide array of variable cell surface stimulatory and inhibitory NK receptors (sNKR and iNKR, respectively). The iNKR are particularly important in terms of NK-cell education. As receptors specific for MHC class I (MHC I) molecules, they are responsible for self-tolerance and adjusting NK-cell reactivity based on the expression level of self-MHC I. The end result of this education is twofold: (1) inhibitory signaling tunes the functional capacity of the NK cell, endowing greater potency with greater education, and (2) education on self allows the NK cell to detect aberrations in MHC I expression, a common occurrence during many viral infections. Many studies have indicated an important role for iNKR and MHC I in disease, making these receptors attractive targets for manipulating NK-cell reactivity in the clinic. A greater understanding of iNKR and their ability to regulate NK cells will provide a basis for future attempts at translating their potential utility into benefits for human health.
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia , Charlottesville, VA , USA ; Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia , Charlottesville, VA , USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Nash
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia , Charlottesville, VA , USA ; Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia , Charlottesville, VA , USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Teoh
authors.affiliation: Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia , Charlottesville, VA , USA ; Division of Nephrology, Department of Medicine, University of Virginia , Charlottesville, VA , USA.
authors.forename: Hairong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia , Charlottesville, VA , USA ; Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia , Charlottesville, VA , USA.
authors.forename: Awndre
authors.initials: A
authors.lastname: Gamache
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia , Charlottesville, VA , USA ; Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia , Charlottesville, VA , USA ; Division of Nephrology, Department of Medicine, University of Virginia , Charlottesville, VA , USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Brown
keywords: NK cells; education; immunity; inhibitory receptors; licensing; virus control