S. Weingarten-Gabbay, Susan Klaeger, S. Sarkizova, Leah R Pearlman, Da-Yuan Chen, Matthew R. Bauer, Hannah B. Taylor, Hasahn L. Conway, C. Tomkins-Tinch, Yaara Finkel, Aharon Nachshon, M. Gentili, Keith D. Rivera, D. Keskin, C. Rice, K. Clauser, N. Hacohen, S. Carr, Jennifer G. Abelin, Mohsan Saeed, Pardis C Sabeti
bioRxiv : the preprint server for biology, 2020
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.
Cited by 13 publications.
Field of study: Biology