Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells.

Nicholas M Adams1, Clair D Geary2, Endi K Santosa2, Dianne Lumaquin2, Jean-Benoît Le Luduec2, Rosa Sottile2, Kattria van der Ploeg2, Joy Hsu2, Benjamin M Whitlock2, Benjamin T Jackson2, Orr-El Weizman2, Morgan Huse2, Katharine C Hsu3, Joseph C Sun4

  1. Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  2. Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  3. Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
  4. Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: sunj@mskcc.org.

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.

Presented by Nicholas Adams

Related talk by Simon Grassman from Viet Buchholz lab [here][1]. [1]:https://jrnlclub.org/research-films/nk-clonal-selection-ly49h

Immunology & MicrobiologyVictoria Fang2019-06 (Jun)