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.
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