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.
Keywords: COVID-19; HLA-E; NK cells; NKG2A; SARS-CoV-2; missing self.
【저자키워드】 COVID-19, SARS-CoV-2, NK cells, HLA-E, NKG2A, missing self., 【초록키워드】 coronavirus disease, Coronavirus disease 2019, coronavirus, NK cell, human leukocyte antigen, peptide, NK cells, in vitro, severe acute respiratory syndrome Coronavirus, virus, Antigen, Protein, infections, Patient, non-structural protein, immune cells, epithelial cells, Innate immune cells, SARS-CoV-2 replication, mechanism, binding, HLA-E, NKG2A, host defense, target cells, target cell, leukocyte, natural, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, infected cells, These data, SARS-CoV-2-infected cells, Defense, ENCODE, inhibitory receptor, Host, susceptible, Prevent, limit, Cell, resulting, detect, activated, contribute, abrogate, respond, lung epithelial cell, innate immune cell, patients with COVID-19, SARS-CoV-2-infected cell, 【제목키워드】 NK cell, ENCODE, abrogate,