How do NK cells notice SARS-CoV-2–infected cells?
SARS-CoV-2 Nsp13 encodes HLA-E–presented peptide VMPLSAPTL that stabilizes HLA-E but blocks NKG2A inhibition, favoring NKG2A+ NK attack.
Source
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
What they did
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.
What they found
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.
The limits
What it doesn't show
Does not prove this pathway alone determines COVID-19 severity in patients, or that boosting NKG2A+ NK cells is a safe therapy.
Key terms
- NKG2A
- Inhibitory NK receptor that binds HLA-E presenting self-peptides.
- HLA-E
- Non-classical MHC molecule presenting peptides to NKG2A/CD94.
- Nsp13
- SARS-CoV-2 non-structural protein 13 encoding the key peptide.
- Missing self
- NK activation when inhibitory self-ligands are absent or non-engaging.
- VMPLSAPTL
- Nsp13 residues 232–240 HLA-E–stabilizing peptide.
Flashcards
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Quiz yourself
The HLA-E–presented SARS-CoV-2 peptide is encoded by:
Common questions
Which viral protein?
Non-structural protein 13 (Nsp13).
Peptide sequence?
VMPLSAPTL (Nsp13 232–240).
Key receptor effect?
Blocks inhibitory HLA-E–NKG2A binding.
Recognition mode?
Missing-self recognition by NK cells.