Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope

Dolton, Garry, Rius, Cristina, Hasan, Md Samiul, Wall, Aaron, Szomolay, Barbara, Behiry, Enas, Whalley, Thomas, Southgate, Joel, Fuller, Anna, Morin, Théo, Topley, Katie, Tan, Li Rong, Goulder, Philip J.R., Spiller, Owen B., Rizkallah, Pierre J., Jones, Lucy C., Connor, Thomas R., Sewell, Andrew K., Bashton, Matthew, Smith, Darren, Nelson, Andrew, Young, Greg, McCann, Clare and The COVID-19 Genomics UK (COG-UK) Consortium, (2022) Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. Cell, 185 (16). 2936-2951.e19. ISSN 0092-8674

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Official URL: https://doi.org/10.1016/j.cell.2022.07.002


We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A∗02+ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Item Type: Article
Additional Information: Matthew Bashton, Andrew Nelson, Clare McCann, Greg Young and Darren Smith are members of the COVID-19 Genomics UK consortium. Funding information: This work was supported by Continuum Life Sciences (CLS) to aid the global COVID-19 effort. CLS provided salary for G.D. and C.R. A.K.S. is a Wellcome Investigator (220295/Z/20/Z) and we acknowledge salary support from Wellcome. E.B. received support from a Wellcome Trust Institutional Strategic Support Fund Fellowship. M.S.H. was part funded by Enara Bio. We are grateful of funding from the Welsh Government through their Senior Research Leaders Scheme to A.K.S. L.C.J. is a Clinical Investigator at Cwm Taf Morgannwg University Health Board (CTMUHB). CTMUHB sponsored and supported the research and provided salary support for L.C.J. T.R.C. acknowledges support from the MRC, which funded the computational resources used by the project (grant reference MR/L015080/1), as well as specific funding from Welsh Government, which provided funds for the sequencing and analysis of Welsh samples used in this study, via Genomics Partnership Wales. UK sequencing has been supported by the COVID-19 Genomics UK Consortium (COG-UK), as well as using genomics data that has partly been funded/generated as part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research and Innovation (UKRI), the National Institute for Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. J.A.S. is funded by the MRC (MR/T030062/1) and TW is funded by the Wellcome Trust (215800/Z/19/Z). The authors gratefully acknowledge the contributors to GISAID whose sequence data enabled an examination of the global spread of P272L. The authors acknowledge Diamond Light Source for time on beamline I04-1 under proposal mx29502.
Uncontrolled Keywords: CD8-Positive T-Lymphocytes, COVID-19, Epitopes, T-Lymphocyte, HLA-A Antigens, Histocompatibility Antigens Class I, Humans, SARS-CoV-2
Subjects: A300 Clinical Medicine
B100 Anatomy, Physiology and Pathology
B200 Pharmacology, Toxicology and Pharmacy
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Rachel Branson
Date Deposited: 22 Feb 2023 09:44
Last Modified: 22 Feb 2023 11:02
URI: https://nrl.northumbria.ac.uk/id/eprint/51464

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