Journal Article

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Nienen, Mikalai, Messerle, Martin, Koenecke, Christian, Thurley, Kevin, Rückert, Timo, Dunst, Josefine, Hofmann, Jörg, Durek, Pawel, Prinz, Immo, Gasparoni, Gilles, Walter, Jörn, Mashreghi, Mir-Farzin, Na, Il-Kang, Haubner, André, Babic, Marina, Romagnani, Chiara, Hemmati, Philipp, Borst, Eva Maria, Blau, Igor Wolfgang, Heinrich, Frederik, Arnold, Renate, Tomic, Adriana, Babel, Nina, Hammer, Quirin, Pietra, Gabriella

2018

Overview

Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C + NK cells has remained unclear. Here we found that adaptive NKG2C + NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C + NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C + NK cell populations among HCMV-seropositive people. NK cells constrain infection by cytomegalovirus. Romagnani and colleagues show that human NKG2C + NK cells recognize distinct HCMV UL40 viral peptides, which can vary among viral isolates. NKG2C + NK cells thereby demonstrate adaptive-like recognition that can discriminate between closely related viral strains.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Antigens / Antiviral agents / Biomedical and Life Sciences / Biomedicine / Control / Cytomegalovirus / Cytomegalovirus - genetics / Cytomegalovirus - immunology / Cytomegalovirus infections / Cytomegalovirus Infections - immunology / Heterogeneity / Humans / Immunology / Infectious Diseases / Inflammation / Killer cells / Killer Cells, Natural - immunology / LACK antigen / Lymphocytes / Natural killer cells / NK Cell Lectin-Like Receptor Subfamily C - immunology / NKG2 antigen / Peptides / Physiological aspects / Population growth / Risk factors / T cell receptors / Viral Proteins - genetics / Viral Proteins - immunology