Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells.

TitleCytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells.
Publication TypeJournal Article
Year of Publication2019
AuthorsAdams NM, Geary CD, Santosa EK, Lumaquin D, Le Luduec J-B, Sottile R, van der Ploeg K, Hsu J, Whitlock BM, Jackson BT, Weizman O-E, Huse M, Hsu KC, Sun JC
JournalImmunity
Volume50
Issue6
Pagination1381-1390.e5
Date Published2019 06 18
ISSN1097-4180
KeywordsAnimals, Cytomegalovirus, Cytomegalovirus Infections, Cytotoxicity, Immunologic, Gene Expression Regulation, Herpesviridae Infections, Host-Pathogen Interactions, Humans, Immunologic Memory, Killer Cells, Natural, Lymphocyte Activation, Mice, Mice, Knockout, Muromegalovirus, NK Cell Lectin-Like Receptor Subfamily A, T-Cell Antigen Receptor Specificity
Abstract

The process of affinity maturation, whereby T and B cells bearing antigen receptors with optimal affinity to the relevant antigen undergo preferential expansion, is a key feature of adaptive immunity. Natural killer (NK) cells are innate lymphocytes capable of "adaptive" responses after cytomegalovirus (CMV) infection. However, whether NK cells are similarly selected on the basis of their avidity for cognate ligand is unknown. Here, we showed that NK cells with the highest avidity for the mouse CMV glycoprotein m157 were preferentially selected to expand and comprise the memory NK cell pool, whereas low-avidity NK cells possessed greater capacity for interferon-γ (IFN-γ) production. Moreover, we provide evidence for avidity selection occurring in human NK cells during human CMV infection. These results delineate how heterogeneity in NK cell avidity diversifies NK cell effector function during antiviral immunity, and how avidity selection might serve to produce the most potent memory NK cells.

DOI10.1016/j.immuni.2019.04.009
Alternate JournalImmunity
PubMed ID31103381
PubMed Central IDPMC6614060
Grant ListR01 AI100874 / AI / NIAID NIH HHS / United States
P01 CA023766 / CA / NCI NIH HHS / United States
R01 AI087644 / AI / NIAID NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
F30 AI136239 / AI / NIAID NIH HHS / United States
R56 AI123658 / AI / NIAID NIH HHS / United States
R01 AI130043 / AI / NIAID NIH HHS / United States

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