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
Affiliations
Christopher Szeto
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Demetra S.M. Chatzileontiadou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Andrea T. Nguyen
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Hannah Sloane
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Christian A. Lobos
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Dhilshan Jayasinghe
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Hanim Halim
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Corey Smith
QIMR Centre for Immunotherapy and Vaccine Development and Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Alan Riboldi-Tunnicliffe
Australian Synchrotron, ANSTO, Clayton, VIC 3168, Australia
Emma J. Grant
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia; Corresponding author
Stephanie Gras
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia; Corresponding author
Summary: 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.
