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The Presentation of SARS-CoV-2 Peptides by the Common HLA-A*02:01 Molecule

35 Pages Posted: 29 Oct 2020 Publication Status: Published

See all articles by Christopher Szeto

Christopher Szeto

Monash University - Department of Biochemistry and Molecular Biology

Demetra S.M. Chatzileontiadou

Monash University - Department of Biochemistry and Molecular Biology

Andrea T. Nguyen

Monash University - Department of Biochemistry and Molecular Biology

Hannah Sloane

Monash University - Department of Biochemistry and Molecular Biology

Christian A. Lobos

Monash University - Department of Biochemistry and Molecular Biology

Dhilshan Jayasinghe

Monash University - Department of Biochemistry and Molecular Biology

Hanim Halim

Monash University - Department of Biochemistry and Molecular Biology

Corey Smith

QIMR Berghofer Medical Research Institute - QIMR Centre for Immunotherapy and Vaccine Development

Alan Riboldi-Tunnicliffe

ANSTO - Australian Synchrotron

Emma J. Grant

Monash University - Department of Biochemistry and Molecular Biology

Stephanie Gras

La Trobe University - Department of Biochemistry & Chemistry

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Abstract

CD8+ T cells are crucial for anti-viral immunity, however, understanding T cell responses requires the identification of viral epitopes, and their presentation by Human Leukocyte Antigens (HLA). To date, few SARS-CoV-2-specific CD8+ T cell epitopes have been described. Internal viral proteins, are typically more conserved than surface proteins, and are often the target of CD8+ T cells. Therefore, we have characterised eight peptides derived from the internal SARS-CoV-2 Nucleocapsid protein predicted to bind HLA-A*02:01, the most common HLA molecule in the global population. We determined not all peptides could form a complex with HLA-A*02:01, and the six crystal structures determined revealed that some peptides adopted a mobile conformation. We therefore provide a molecular understanding of SARS-CoV-2 CD8+ T cell epitopes. Furthermore, we show that there is limited pre-existing CD8+ T cell response towards these epitopes in unexposed individuals. Together, these data show that SARS-CoV-2 Nucleocapsid might not contain potent epitopes restricted to HLA-A*02:01.

Funding: This work was funded by the Australian National Health and Medical Research Council (NHMRC), C.S. and D.S.M.C. are supported with an AINSE Early Career Research Grant, E.J.G. is supported by an NHMRC CJ Martin Fellowship (#1110429) and S.G. is supported by an NHMRC Senior Research Fellowship (#1159272).

Conflict of Interest: The authors have no competing interests.

Ethical Approval: All work using human samples was approved by the Monash University Human Ethics Committee (#19079 and #18380).

Suggested Citation

Szeto, Christopher and Chatzileontiadou, Demetra S.M. and Nguyen, Andrea T. and Sloane, Hannah and Lobos, Christian A. and Jayasinghe, Dhilshan and Halim, Hanim and Smith, Corey and Riboldi-Tunnicliffe, Alan and Grant, Emma J. and Gras, Stephanie, The Presentation of SARS-CoV-2 Peptides by the Common HLA-A*02:01 Molecule. Available at SSRN: https://ssrn.com/abstract=3721718 or http://dx.doi.org/10.2139/ssrn.3721718
This version of the paper has not been formally peer reviewed.

Christopher Szeto

Monash University - Department of Biochemistry and Molecular Biology

Clayton, Victoria
Australia

Demetra S.M. Chatzileontiadou

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Andrea T. Nguyen

Monash University - Department of Biochemistry and Molecular Biology

Clayton, Victoria
Australia

Hannah Sloane

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Christian A. Lobos

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Dhilshan Jayasinghe

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Hanim Halim

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Corey Smith

QIMR Berghofer Medical Research Institute - QIMR Centre for Immunotherapy and Vaccine Development

Brisbane, Queensland
Australia

Alan Riboldi-Tunnicliffe

ANSTO - Australian Synchrotron ( email )

Emma J. Grant

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Stephanie Gras (Contact Author)

La Trobe University - Department of Biochemistry & Chemistry ( email )

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