SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs

Weingarten-Gabbay, S.; Klaeger, S.; Sarkizova, S.; Pearlman, L. R.; Chen, D.-Y.; Bauer, M. R.; Taylor, H. B.; Conway, H. L.; Tomkins-Tinch, C. H.; Finkel, Y.; Nachshon, A.; Gentili, M.; Rivera, K. D.; Keskin, D. B.; Rice, C. M.; Clauser, K. R.; Hacohen, N.; Carr, S. A.; Abelin, J. G.; Saeed, M.; Sabeti, P. C.

doi:10.1101/2020.10.02.324145

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bioRxiv · 10.1101/2020.10.02.324145

SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs

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Abstract

T cell-mediated immunity may play a critical role in controlling and establishing protective immunity against SARS-CoV-2 infection; yet the repertoire of viral epitopes responsible for T cell response activation remains mostly unknown. Identification of viral peptides presented on class I human leukocyte antigen (HLA-I) can reveal epitopes for recognition by cytotoxic T cells and potential incorporation into vaccines. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two human cell lines at different times post-infection using mass spectrometry. We found HLA-I peptides derived not only from canonical ORFs, but also from internal out-of-frame ORFs in Spike and Nucleoprotein not captured by current vaccines. Proteomics analyses of infected cells revealed that SARS-CoV-2 may interfere with antigen processing and immune signaling pathways. Based on the endogenously processed and presented viral peptides that we identified, we estimate that a pool of 24 peptides would provide one or more peptides for presentation by at least one HLA allele in 99% of the human population. These biological insights and the list of naturally presented SARS-CoV-2 peptides will facilitate data-driven selection of peptides for immune monitoring and vaccine development.

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Weingarten-Gabbay, S., Klaeger, S., Sarkizova, S., Pearlman, L. R., Chen, D.-Y., Bauer, M. R., Taylor, H. B., Conway, H. L., Tomkins-Tinch, C. H., Finkel, Y., Nachshon, A., Gentili, M., Rivera, K. D., Keskin, D. B., Rice, C. M., Clauser, K. R., Hacohen, N., Carr, S. A., Abelin, J. G., Saeed, M., Sabeti, P. C.. 2020-10-02. SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs. https://doi.org/10.1101/2020.10.02.324145

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