The presentation of SARS-CoV-2 peptides by the common HLA-A∗02:01 molecule

Christopher Szeto; Demetra S M Chatzileontiadou; Andrea T Nguyen; Hannah Sloane; Christian A Lobos; Dhilshan Jayasinghe; Hanim Halim; Corey Smith; Alan Riboldi-Tunnicliffe; Emma J Grant; Stephanie Gras

doi:10.1016/j.isci.2021.102096

The presentation of SARS-CoV-2 peptides by the common HLA-A^∗02:01 molecule

iScience. 2021 Feb 19;24(2):102096. doi: 10.1016/j.isci.2021.102096. Epub 2021 Jan 22.

Authors

Christopher Szeto^{1

2}, Demetra S M Chatzileontiadou^{1

2}, Andrea T Nguyen^{1

2}, Hannah Sloane^{1

2}, Christian A Lobos^{1

2}, Dhilshan Jayasinghe^{1

2}, Hanim Halim¹, Corey Smith³, Alan Riboldi-Tunnicliffe⁴, Emma J Grant^{1

2}, Stephanie Gras^{1

2

5}

Affiliations

¹ Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
² Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia.
³ QIMR Centre for Immunotherapy and Vaccine Development and Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
⁴ Australian Synchrotron, ANSTO, Clayton, VIC 3168, Australia.
⁵ Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.

Abstract

CD8+ T cells are crucial for anti-viral immunity; however, understanding T cell responses requires the identification of epitopes presented 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 characterized 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 toward 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.

Keywords: immunology; structural biology; virology.