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Publication : Control of Viral Infection by Natural Killer Cell Inhibitory Receptors.

First Author  Parikh BA Year  2020
Journal  Cell Rep Volume  32
Issue  4 Pages  107969
PubMed ID  32726632 Mgi Jnum  J:295190
Mgi Id  MGI:6458195 Doi  10.1016/j.celrep.2020.107969
Citation  Parikh BA, et al. (2020) Control of Viral Infection by Natural Killer Cell Inhibitory Receptors. Cell Rep 32(4):107969
abstractText  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.
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