Abstract
Natural Killer (NK) cell functionality is controlled by inhibitory receptors that recognize self-MHC class I. NK cells that do not interact with self-MHC class I are hypo-responsive to many stimuli and fail to reject MHC class I-deficient cells. Thus, although the mechanisms are unknown, interactions with MHC class I "licensed" NK cells respond efficiently. Surprisingly, these licensed NK cells fail to control viral infection. During mouse cytomegalovirus (MCMV) infection, SHP-1 signaling downstream of inhibitory receptors for MHC class I limits NK cell proliferation. Interactions with MHC class I prevent licensed NK cells from controlling of MCMV replication and pathogenesis; rather, it is the unlicensed NK cells that are not inhibited by self-MHC class I that efficiently control MCMV infection. Therefore, the licensing hypothesis is not sufficient to explain NK cell functionality during viral infection.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Cell Proliferation
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Cytomegalovirus Infections / genetics
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Cytomegalovirus Infections / immunology*
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Cytomegalovirus Infections / virology
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Histocompatibility Antigens Class I* / genetics
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Histocompatibility Antigens Class I* / immunology
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Humans
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Immunity, Innate*
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Muromegalovirus / physiology*
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / immunology
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
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Receptors, Natural Killer Cell / genetics
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Receptors, Natural Killer Cell / immunology
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Receptors, Natural Killer Cell / metabolism*
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Signal Transduction / genetics
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Signal Transduction / immunology
Substances
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Histocompatibility Antigens Class I
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Receptors, Natural Killer Cell
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Ptpn6 protein, mouse