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Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

  1. Author:
    Weingarten-Gabbay, Shira
    Klaeger, Susan
    Sarkizova, Siranush
    Pearlman, Leah R.
    Chen, Da-Yuan
    Gallagher, Kathleen M. E.
    Bauer, Matthew R.
    Taylor, Hannah B.
    Dunn, W. Augustine
    Tarr, Christina
    Sidney, John
    Rachimi, Suzanna
    Conway, Hasahn L.
    Katsis, Katelin
    Wang, Yuntong
    Leistritz-Edwards, Del
    Durkin, Melissa R.
    Tomkins-Tinch, Christopher H.
    Finkel, Yaara
    Nachshon, Aharon
    Gentili, Matteo
    Rivera, Keith D.
    Carulli, Isabel P.
    Chea, Vipheaviny A.
    Chandrashekar, Abishek
    Bozkus, Cansu Cimen
    Carrington,Mary
    Bhardwaj, Nina
    Barouch, Dan H.
    Sette, Alessandro
    Maus, Marcela
    Rice, Charles M.
    Clauser, Karl R.
    Keskin, Derin B.
    Pregibon, Daniel C.
    Hacohen, Nir
    Carr, Steven A.
    Abelin, Jennifer G.
    Saeed, Mohsan
    Sabeti, Pardis C.

  2. Author Address

    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.Boston Univ, Natl Emerging Infect Dis Labs, Boston, MA 02215 USA.Massachusetts Gen Hosp, Cellular Immunotherapy Program, Charlestown, MA 02129 USA.Massachusetts Gen Hosp, Canc Ctr, Charlestown, MA 02129 USA.Harvard Med Sch, Boston, MA 02115 USA.Harvard Med Sch, Harvard Program Biol & Biomed Sci, Boston, MA 02115 USA.Repertoire Immune Med, Cambridge, MA 02139 USA.La Jolla Inst Immunol LJI, Ctr Infect Dis & Vaccine Res, La Jolla, CA 92037 USA.Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.Dana Farber Canc Inst, Translat Immunogen Lab, Boston, MA 02115 USA.Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.Mt Sinai Hosp, Icahn Sch Med, Dept Hematol & Med Oncol, New York, NY 10029 USA.Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.NCI, Basic Sci Program, Frederick Natl Lab Canc Res, Lab Integrat Canc Immunol, Bethesda, MD 20892 USA.Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA.Massachusetts Consortium Pathogen Readiness, Boston, MA USA.Univ Calif San Diego, Dept Med, Div Infect Dis & Global Publ Hlth, La Jolla, CA 92037 USA.Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02139 USA.Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.Boston Univ, Metropolitan Coll, Hlth Informat Lab, Boston, MA 02215 USA.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA USA.Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA.Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
    1. Year: 2021
    2. Date: Jul 22
  2. Journal: CELL
  3. CELL PRESS,
    1. 184
    2. 15
    3. Pages: 3962-3980.e17
  5. Type of Article: Article
  6. Article Number: ARTN e17
  7. ISSN: 0092-8674
  1. Abstract:

    T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.

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External Sources

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  2. DOI: 10.1016/j.cell.2021.05.046
  3. View record in Web of Science®
  4. WOS: 000676120800012

Library Notes

  1. Fiscal Year: FY2020-2021
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