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 Bashton; Darren Smith; Andrew Nelson; Gregory R. Young; Clare McCann

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, 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 journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	2936-2951.e19
Number of pages	36
Journal	Cell
Volume	185
Issue number	16
Early online date	14 Jul 2022
DOIs	https://doi.org/10.1016/j.cell.2022.07.002
Publication status	Published - 4 Aug 2022

Keywords

CD8-Positive T-Lymphocytes
COVID-19
Epitopes, T-Lymphocyte
HLA-A Antigens
Histocompatibility Antigens Class I
Humans
SARS-CoV-2

UN SDGs

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

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Cite this

The COVID-19 Genomics UK (COG-UK) Consortium, Dolton, G., Rius, C., Hasan, M. S., Wall, A., Szomolay, B., Behiry, E., Whalley, T., Southgate, J., Fuller, A., Morin, T., Topley, K., Tan, L. R., Goulder, P. J. R., Spiller, O. B., Rizkallah, P. J., Jones, L. C., Connor, T. R., Sewell, A. K., ... McCann, C. (2022). Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. Cell, 185(16), 2936-2951.e19. https://doi.org/10.1016/j.cell.2022.07.002

@article{9cd643fd54844ec0a0558c742a7237b2,

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-Positive T-Lymphocytes, COVID-19, Epitopes, T-Lymphocyte, HLA-A Antigens, Histocompatibility Antigens Class I, Humans, SARS-CoV-2",

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.\} and Matthew Bashton and Darren Smith and Andrew Nelson and Young, \{Gregory R.\} and Clare McCann",

note = "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.",

year = "2022",

month = aug,

day = "4",

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

language = "English",

volume = "185",

pages = "2936--2951.e19",

journal = "Cell",

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The COVID-19 Genomics UK (COG-UK) Consortium, Dolton, G, Rius, C, Hasan, MS, Wall, A, Szomolay, B, Behiry, E, Whalley, T, Southgate, J, Fuller, A, Morin, T, Topley, K, Tan, LR, Goulder, PJR, Spiller, OB, Rizkallah, PJ, Jones, LC, Connor, TR, Sewell, AK, Bashton, M , Smith, D , Nelson, A, Young, GR & McCann, C 2022, 'Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope', Cell, vol. 185, no. 16, pp. 2936-2951.e19. https://doi.org/10.1016/j.cell.2022.07.002

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T1 - Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope

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.

AU - Bashton, Matthew

AU - Smith, Darren

AU - Nelson, Andrew

AU - Young, Gregory R.

AU - McCann, Clare

N1 - 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.

PY - 2022/8/4

Y1 - 2022/8/4

N2 - 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.

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.

KW - CD8-Positive T-Lymphocytes

KW - COVID-19

KW - Epitopes, T-Lymphocyte

KW - HLA-A Antigens

KW - Histocompatibility Antigens Class I

KW - Humans

KW - SARS-CoV-2

UR - https://www.scopus.com/pages/publications/85135599451

U2 - 10.1016/j.cell.2022.07.002

DO - 10.1016/j.cell.2022.07.002

M3 - Article

C2 - 35931021

SN - 0092-8674

VL - 185

SP - 2936-2951.e19

JO - Cell

JF - Cell

IS - 16

ER -