Control of Viral Infection by Natural Killer Cell Inhibitory Receptors.
Major histocompatibility complex class I (MHC-I)-restricted immune responses are largely attributed to cytotoxic T lymphocytes (CTLs). However, natural killer (NK) cells, as predicted by the missing-self hypothesis, have opposing requirements for MHC-I, suggesting that they may also demonstrate MHC-I-restricted effects. In mice, the Ly49 inhibitory receptors prevent NK cell killing of missing-self targets in effector responses, and they have a proposed second function in licensing or educating NK cells via self-MHC-I in vivo. Here we show MHC-I-restricted control of murine cytomegalovirus (MCMV) infection in vivo that is NK cell dependent. Using mice lacking specific Ly49 receptors, we show that control of MCMV requires inhibitory Ly49 receptors and an inhibitory signaling motif and the capacity for MCMV to downregulate MHC-I. Taken together, these data provide definitive evidence that the inhibitory receptors are required for missing-self rejection and are relevant to MHC-I-restricted NK cell control of a viral infection in vivo.
['Parikh|Bijal A|BA|', 'Bern|Michael D|MD|', 'Piersma|Sytse J|SJ|', 'Yang|Liping|L|', 'Beckman|Diana L|DL|', 'Poursine-Laurent|Jennifer|J|', 'Plougastel-Douglas|Béatrice|B|', 'Yokoyama|Wayne M|WM|']
D000818:Animals D000950:Antigens, Ly D003586:Cytomegalovirus Infections D015395:Histocompatibility Antigens Class I D007694:Killer Cells, Natural D051379:Mice D008810:Mice, Inbred C57BL D018146:Muromegalovirus D055650:NK Cell Lectin-Like Receptor Subfamily A D055607:Receptors, Natural Killer Cell D014777:Virus Diseases
inhibitory receptors missing-self Ly49 cytomegalovirus ITIM