Profiling of the SARS-CoV-2 HLA-I Peptidome Reveals T Cell Epitopes from Out-of-Frame ORFs

DOI: https : //doi.org/10.1016/j.cell.2021.05.046

Commentary

T-cell immunity plays an important role in the control of SARS-CoV-2 infection, but the repertoire of viral epitopes naturally processed and presented by HLA class I remains uncharacterized, according to

In this study, we use mass spectrometry to report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times after infection; the HLA-I peptides are derived not only from standard ORFs, but also from the internal Spike and Nucleocapsid, which are not captured by current vaccines. The HLA-I peptides were found to be derived not only from the standard ORFs but also from extraframe ORFs inside Spike and Nucleocapsid that are not captured by current vaccines. Several peptides from the extraframe ORFs elicited T-cell responses in humanized mouse models and COVID-19 patients that exceeded the responses to standard peptides containing some of the strongest epitopes reported to date.

Whole proteome analysis of infected cells revealed that early expressed viral proteins further contribute to HLA-I presentation and immunogenicity.

In other words, the T-cell nature of human immunity is believed to have a major role in controlling infection, but there is a lack of response to SARS-CoV-2.

The study stated that vaccine designs should be re-evaluated based on these new information.