RT Journal Article
SR Electronic
T1 Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.15.456333
DO 10.1101/2021.08.15.456333
A1 Christopher Szeto
A1 Andrea T. Nguyen
A1 Christian A. Lobos
A1 Dimitra S.M. Chatzileontiadou
A1 Dhilshan Jaya-singhe
A1 Emma J. Grant
A1 Alan Riboldi-Tunnicliffe
A1 Corey Smith
A1 Stephanie Gras
YR 2021
UL http://biorxiv.org/content/early/2021/08/16/2021.08.15.456333.abstract
AB 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.