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

Dolton, Garry, Rius, Cristina, Hasan, Md Samiul, Wall, Aaron, Szomolay, Barbara ORCID: https://orcid.org/0000-0002-5375-5533, Behiry, Enas, Whalley, Thomas, Southgate, Joel, Fuller, Anna, Morin, Théo, Topley, Katie, Tan, Li Rong, Goulder, Philip J.R., Spiller, Owen B. ORCID: https://orcid.org/0000-0002-9117-6911, Rizkallah, Pierre J. ORCID: https://orcid.org/0000-0002-9290-0369, Jones, Lucy C. ORCID: https://orcid.org/0000-0002-3872-4376, Connor, Thomas R. ORCID: https://orcid.org/0000-0003-2394-6504 and Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 2022. Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. Cell 185 (16) , pp. 2936-2951. 10.1016/j.cell.2022.07.002

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Abstract

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
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher:	Elsevier
ISSN:	0092-8674
Funders:	Wellcome Trust
Date of First Compliant Deposit:	15 August 2022
Date of Acceptance:	7 July 2022
Last Modified:	15 Jan 2024 12:15
URI:	https://orca.cardiff.ac.uk/id/eprint/151914

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