Molecular Basis of a Dominant SARS-CoV-2 Spike-Derived Epitope Presented by HLA-A*02:01 Recognised by a Public TCR
Christopher Szeto,
Andrea T. Nguyen,
Christian A. Lobos,
Demetra S. M. Chatzileontiadou,
Dhilshan Jayasinghe,
Emma J. Grant,
Alan Riboldi-Tunnicliffe,
Corey Smith,
Stephanie Gras
Affiliations
Christopher Szeto
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Andrea T. Nguyen
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Christian A. Lobos
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Demetra S. M. Chatzileontiadou
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Dhilshan Jayasinghe
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Emma J. Grant
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Alan Riboldi-Tunnicliffe
Australian Synchrotron, ANSTO, Clayton, VIC 3168, Australia
Corey Smith
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Stephanie Gras
Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
The data currently available on how the immune system recognises the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus; however, we lack data on how T cells are able to recognise this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.
