Description
Cytotoxic T lymphocytes (CTL) find and kill cells infected with viruses by examining
viral epitopes presented by MHC class I molecules on the surface of the cell. In
the context of SARS-CoV-2, infected patients have elicited CTL responses by
showing higher levels of granzyme B, perforin and IFN-gamma.
Rapid rate of mutation in SARS-CoV-2 may hinder the presentation of peptides by
MHC-I molecules thereby evading T cell response.
Agerer et al. performed deep sequencing of viral
genomes from several patients and identified mutations that were observed in
Nucleocapsid (N), ORF1ab, Membrane (M), and Envelope (E) proteins. This track
includes 194 mutants spanning 305 T-cell epitopes restricted to HLA-A*02:01 and
HLA-B*40:01.
Methods
In this study, deep sequencing was performed on virus samples from Austria. To
identify mutant epitopes, MHC-I binding assays were performed. Subsequently,
PBMCs collected from HLA-A*02:01 and HLA-B*40:01 typed, COVID-19 patients were
subjected to functional assays. A more detailed description of the methodology
is decribed in the original article.
References
Agerer B, Koblischke M, Gudipati V, Montaño-Gutierrez LF, Smyth M, Popa A, Genger JW, Endler L,
Florian DM, Mühlgrabner V et al.
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell
responses.
Sci Immunol. 2021 Mar 4;6(57).
PMID: 33664060
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