@article {Szeto2021.08.15.456333, author = {Christopher Szeto and Andrea T. Nguyen and Christian A. Lobos and Dimitra S.M. Chatzileontiadou and Dhilshan Jaya-singhe and Emma J. Grant and Alan Riboldi-Tunnicliffe and Corey Smith and Stephanie Gras}, title = {Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR}, elocation-id = {2021.08.15.456333}, year = {2021}, doi = {10.1101/2021.08.15.456333}, publisher = {Cold Spring Harbor Laboratory}, 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.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/08/16/2021.08.15.456333}, eprint = {https://www.biorxiv.org/content/early/2021/08/16/2021.08.15.456333.full.pdf}, journal = {bioRxiv} }