Hammer Q, Dunst J, Christ W, Picarazzi F, Wendorff M, Momayyezi P, Huhn O, Netskar HK, Maleki KT, García M, Sekine T, Sohlberg E, Azzimato V, Aouadi M, Karolinska COVID-19 Study Group , Severe COVID-19 GWAS Group , Degenhardt F, Franke A, Spallotta F, Mori M, Michaëlsson J, Björkström NK, Rückert T, Romagnani C, Horowitz A, Klingström J, Ljunggren H, Malmberg K
Cell Rep - (-) 110503 [2022-02-21; online 2022-02-21]
Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.