ABSTRACT
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.
Subject(s)
COVID-19 , Histocompatibility Antigens Class I , Killer Cells, Natural , Methyltransferases , NK Cell Lectin-Like Receptor Subfamily C , RNA Helicases , SARS-CoV-2 , Viral Nonstructural Proteins , COVID-19/immunology , Histocompatibility Antigens Class I/immunology , Humans , Killer Cells, Natural/immunology , Methyltransferases/immunology , NK Cell Lectin-Like Receptor Subfamily C/immunology , NK Cell Lectin-Like Receptor Subfamily C/metabolism , Peptides/metabolism , RNA Helicases/immunology , Viral Nonstructural Proteins/immunologyABSTRACT
Natural killer (NK) cells eliminate virus-infected cells. Hammer et al. show that SARS-CoV-2 encodes for a peptide that does not bind to an inhibitory receptor of NK cells, thereby facilitating NK cell activation. This missing self recognition could enable NK cells to detect and kill SARS-CoV-2-infected cells.