title: Natural killer cell licensing during viral infection.
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.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Orr
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000502:physiology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D055607:Receptors, Natural Killer Cell; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse