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Natural Killer Cell Licensing During Viral Infection

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Crossroads between Innate and Adaptive Immunity III

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 780))

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.

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Acknowledgements

M.T.O is an Irvington Postdoctoral Fellow of the Cancer Research Institute. L.L.L. is an American Cancer Society Professor and is supported by NIH grants AI068129, CA095137, and AI066897.

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Authors and Affiliations

  1. Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, 513 Parnassus Ave., HSE 1001G, San Francisco, CA, 94143–0414, USA

    Lewis L. Lanier

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  1. Mark T. Orr
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Correspondence to Lewis L. Lanier .

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Editors and Affiliations

  1. Emory Vaccine Center &, Yerkes National Primate Research Center, Emory University, Gatewood Rd. 954, Atlanta, 30329, Georgia, USA

    Bali Pulendran

  2. College of Medicine, Department Microbiology & Immunology, Drexel University, Queen Lane 2900, Philadelphia, 19129, Pennsylvania, USA

    Peter D. Katsikis

  3. , Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immun, Athena Circle 9420, La Jolla, 92037, USA

    Stephen P. Schoenberger

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Orr, M.T., Lanier, L.L. (2011). Natural Killer Cell Licensing During Viral Infection. In: Pulendran, B., Katsikis, P., Schoenberger, S. (eds) Crossroads between Innate and Adaptive Immunity III. Advances in Experimental Medicine and Biology, vol 780. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5632-3_4

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