Cytomegalovirus infection drives avidity selection of natural killer cells Journal Article


Authors: Adams, N. M.; Geary, C. D.; Santosa, E. K.; Lumaquin, D.; Le Luduec, J. B.; Sottile, R.; van der Ploeg, K.; Hsu, J.; Whitlock, B. M.; Jackson, B. T.; Weizman, O. E.; Huse, M.; Hsu, K. C.; Sun, J. C.
Article Title: Cytomegalovirus infection drives avidity selection of natural killer cells
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. NK cells are innate lymphocytes capable of “adaptive” responses after infection, but whether they undergo avidity selection is unknown. Adams et al. report that diversity in antigen receptor Ly49H expression drives NK cell functional heterogeneity during MCMV infection with high-avidity NK cells being selected to dominate the adaptive response. © 2019 Elsevier Inc.
Keywords: cytomegalovirus; selection; heterogeneity; nk cells; viral infection
Journal Title: Immunity
Volume: 50
Issue: 6
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2019-06-18
Start Page: 1381
End Page: 1390.e5
Language: English
DOI: 10.1016/j.immuni.2019.04.009
PUBMED: 31103381
PROVIDER: scopus
PMCID: PMC6614060
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Katharine C Hsu
    184 Hsu
  2. Morgan Huse
    68 Huse
  3. Joseph C Sun
    130 Sun
  4. Clair   Geary
    14 Geary
  5. Orrel   Weizman
    11 Weizman
  6. Nicholas M Adams
    19 Adams
  7. Endi Santosa
    13 Santosa
  8. Joy Hsu
    1 Hsu