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

The COVID-19 Genomics UK (COG-UK) Consortium, Garry Dolton, Cristina Rius, Md Samiul Hasan, Aaron Wall, Barbara Szomolay, Enas Behiry, Thomas Whalley, Joel Southgate, Anna Fuller, Théo Morin, Katie Topley, Li Rong Tan, Philip J R Goulder, Owen B Spiller, Pierre J Rizkallah, Lucy C Jones, Thomas R. Connor, Andrew K. Sewell*, Matthew BashtonDarren Smith, Andrew Nelson, Gregory R. Young, Clare McCann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2936-2951.e19
Number of pages36
JournalCell
Volume185
Issue number16
Early online date14 Jul 2022
DOIs
Publication statusPublished - 4 Aug 2022

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