The HLA-II immunopeptidome of SARS-CoV-2

Shira Weingarten-Gabbay; Da-Yuan Chen; Siranush Sarkizova; Hannah B Taylor; Matteo Gentili; Gabrielle M Hernandez; Leah R Pearlman; Matthew R Bauer; Charles M Rice; Karl R Clauser; Nir Hacohen; Steven A Carr; Jennifer G Abelin; Mohsan Saeed; Pardis C Sabeti

doi:10.1016/j.celrep.2023.113596

The HLA-II immunopeptidome of SARS-CoV-2

Cell Rep. 2024 Jan 23;43(1):113596. doi: 10.1016/j.celrep.2023.113596. Epub 2023 Dec 20.

Authors

Affiliations

¹ Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA. Electronic address: shirawg@broadinstitute.org.
² Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
³ Broad Institute of MIT and Harvard University, Cambridge, MA, USA.
⁴ Harvard Program in Biological and Biomedical Sciences, Division of Medical Sciences, Harvard University Medical School, Boston, MA, USA.
⁵ Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
⁶ Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
⁷ Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.

Abstract

Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames. Most HLA-II peptides colocalize with known CD4⁺ T cell epitopes in coronavirus disease 2019 patients, including 2 reported immunodominant regions in the SARS-CoV-2 membrane protein. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and nonstructural and noncanonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4⁺ and CD8⁺ T cell epitopes to maximize vaccine effectiveness.

Keywords: CD4(+) T cell; CP: Immunology; CP: Microbiology; HLA-II; SARS-CoV-2; antigen processing and presentation; immunity; immunopeptidome; noncanonical protein; viral antigen.

MeSH terms

CD8-Positive T-Lymphocytes
COVID-19*
Epitopes, T-Lymphocyte
HLA Antigens
Histocompatibility Antigens
Histocompatibility Antigens Class I
Humans
Peptides
SARS-CoV-2*

Substances

Epitopes, T-Lymphocyte
Histocompatibility Antigens Class I
HLA Antigens
Histocompatibility Antigens
Peptides

Abstract

MeSH terms

Substances

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