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

The COVID-19 Genomics UK (COG-UK) consortium

doi:10.1016/j.cell.2022.07.002

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

The COVID-19 Genomics UK (COG-UK) consortium

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein_269-277 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 language	English
Pages (from-to)	2936-2951.e19
Journal	Cell
Volume	185
Issue number	16
DOIs	https://doi.org/10.1016/j.cell.2022.07.002
Publication status	Published - 4 Aug 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

CD8 T cell
COVID-19
SARS-CoV-2
T cell
T cell receptors
immune escape
peptide-HLA
phylogenetic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2022.07.002

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title = "Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope",

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.",

keywords = "CD8 T cell, COVID-19, SARS-CoV-2, T cell, T cell receptors, immune escape, peptide-HLA, phylogenetic",

author = "{The COVID-19 Genomics UK (COG-UK) consortium} and Garry Dolton and Cristina Rius and Hasan, {Md Samiul} and Aaron Wall and Barbara Szomolay and Enas Behiry and Thomas Whalley and Joel Southgate and Anna Fuller and Th{\'e}o Morin and Katie Topley and Tan, {Li Rong} and Goulder, {Philip J.R.} and Spiller, {Owen B.} and Rizkallah, {Pierre J.} and Jones, {Lucy C.} and Connor, {Thomas R.} and Sewell, {Andrew K.}",

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doi = "10.1016/j.cell.2022.07.002",

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AU - The COVID-19 Genomics UK (COG-UK) consortium

AU - Dolton, Garry

AU - Rius, Cristina

AU - Hasan, Md Samiul

AU - Wall, Aaron

AU - Szomolay, Barbara

AU - Behiry, Enas

AU - Whalley, Thomas

AU - Southgate, Joel

AU - Fuller, Anna

AU - Morin, Théo

AU - Topley, Katie

AU - Tan, Li Rong

AU - Goulder, Philip J.R.

AU - Spiller, Owen B.

AU - Rizkallah, Pierre J.

AU - Jones, Lucy C.

AU - Connor, Thomas R.

AU - Sewell, Andrew K.

PY - 2022/8/4

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AB - 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.

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KW - immune escape

KW - peptide-HLA

KW - phylogenetic

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

Abstract

Bibliographical note

Keywords

UN SDGs

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