immunology
How do NK cells notice SARS-CoV-2–infected cells?
Open access · cc by · source: Europe PMC
SARS-CoV-2 Nsp13 encodes HLA-E–presented peptide VMPLSAPTL that stabilizes HLA-E but blocks NKG2A inhibition, favoring NKG2A+ NK attack.
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How do NK cells notice SARS-CoV-2–infected cells?
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Nsp13 232–240 VMPLSAPTL had predicted score 0.717.
Nsp13 232–240 ; VMPLSAPTL; score 0.717
Which SARS-CoV-2 protein encodes the HLA-E peptide?
the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E)
Key findings
Nsp13 232–240 (VMPLSAPTL) was a top predicted binder. Unlike self-peptides, the viral peptide prevents HLA-E–NKG2A inhibitory binding, rendering targets susceptible to NK cells (missing-self). NKG2A-expressing NK cells are particularly activated in COVID-19 and can limit replication in vitro.
Methodology
Predicted HLA-E–binding SARS-CoV-2 nonamers, tested peptide stabilization of HLA-E, assessed NKG2A binding/inhibition, and linked findings to NKG2A+ NK activation in COVID-19 and in vitro control of infected lung epithelial cells.
Limitations
Does not prove this pathway alone determines COVID-19 severity in patients, or that boosting NKG2A+ NK cells is a safe therapy.
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