Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR

Szeto, C.; Nguyen, A. T.; Lobos, C. A.; Chatzileontiadou, D. S.; Jayasinghe, D.; Grant, E. J.; Riboldi-Tunnicliffe, A.; Smith, C.; Gras, S.

doi:10.1101/2021.08.15.456333

bioRxiv · 10.1101/2021.08.15.456333

Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR

Szeto, C.·Nguyen, A. T.·Lobos, C. A.·Chatzileontiadou, D. S.·Jayasinghe, D.·Grant, E. J.·Riboldi-Tunnicliffe, A.·Smith, C.·Gras, S.

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Abstract

The data currently available on how the immune system recognizes 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, we are lacking data on how T cells are able to recognize 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.

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Szeto, C., Nguyen, A. T., Lobos, C. A., Chatzileontiadou, D. S., Jayasinghe, D., Grant, E. J., Riboldi-Tunnicliffe, A., Smith, C., Gras, S.. 2021-08-16. Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR. https://doi.org/10.1101/2021.08.15.456333

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