Control of Viral Infection by Natural Killer Cell Inhibitory Receptors
Bijal A. Parikh,
Michael D. Bern,
Sytse J. Piersma,
Liping Yang,
Diana L. Beckman,
Jennifer Poursine-Laurent,
Béatrice Plougastel-Douglas,
Wayne M. Yokoyama
Affiliations
Bijal A. Parikh
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Michael D. Bern
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Sytse J. Piersma
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Liping Yang
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Diana L. Beckman
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Jennifer Poursine-Laurent
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Béatrice Plougastel-Douglas
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Wayne M. Yokoyama
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Summary: 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.
