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Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs.
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 V; 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.
  • Weingarten-Gabbay S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: shirawg@broadinstitute.org.
  • Klaeger S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: sklaeger@broadinstitute.org.
  • Sarkizova S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Pearlman LR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Chen DY; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Gallagher KME; Cellular Immunotherapy Program and Cancer Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Bauer MR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
  • Taylor HB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Dunn WA; Repertoire Immune Medicines, Cambridge, MA 02139, USA.
  • Tarr C; Repertoire Immune Medicines, Cambridge, MA 02139, USA.
  • Sidney J; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
  • Rachimi S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Conway HL; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Katsis K; Cellular Immunotherapy Program and Cancer Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Wang Y; Repertoire Immune Medicines, Cambridge, MA 02139, USA.
  • Leistritz-Edwards D; Repertoire Immune Medicines, Cambridge, MA 02139, USA.
  • Durkin MR; Repertoire Immune Medicines, Cambridge, MA 02139, USA.
  • Tomkins-Tinch CH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
  • Finkel Y; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Nachshon A; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Gentili M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rivera KD; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Carulli IP; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Chea VA; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Chandrashekar A; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Bozkus CC; Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
  • Carrington M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA.
  • Bhardwaj N; Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
  • Barouch DH; Harvard Medical School, Boston, MA 02115, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Sette A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
  • Maus MV; Cellular Immunotherapy Program and Cancer Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Massachusetts General Hospital,
  • Rice CM; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • Clauser KR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Keskin DB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA; Health Informatics Lab, Metropolitan College, Boston University, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston
  • Pregibon DC; Repertoire Immune Medicines, Cambridge, MA 02139, USA.
  • Hacohen N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Carr SA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Abelin JG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Saeed M; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA. Electronic address: msaeed1@bu.edu.
  • Sabeti PC; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of
Cell ; 184(15): 3962-3980.e17, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1252549
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptides / Histocompatibility Antigens Class I / Open Reading Frames / Epitopes, T-Lymphocyte / Proteome / SARS-CoV-2 Topics: Vaccines Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptides / Histocompatibility Antigens Class I / Open Reading Frames / Epitopes, T-Lymphocyte / Proteome / SARS-CoV-2 Topics: Vaccines Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article