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

Garry Dolton; Cristina Rius; Md Samiul Hasan; Aaron Wall; Barbara Szomolay; Enas Behiry; Thomas Whalley; Joel Southgate; Anna Fuller; COVID-19 Genomics UK (COG-UK) consortium; 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

doi:10.1016/j.cell.2022.07.002

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

Garry Dolton, Cristina Rius, Md Samiul Hasan, Aaron Wall, Barbara Szomolay, Enas Behiry, Thomas Whalley, Joel Southgate, Anna Fuller, COVID-19 Genomics UK (COG-UK) consortium, 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^*

^*Awdur cyfatebol y gwaith hwn

Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid

50 Wedi eu Llwytho i Lawr (Pure)

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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.

Iaith wreiddiol	Saesneg
Tudalennau (o-i)	2936-2951.e19
Nifer y tudalennau	35
Cyfnodolyn	Cell
Cyfrol	185
Rhif cyhoeddi	16
Dyddiad ar-lein cynnar	14 Gorff 2022
Dynodwyr Gwrthrych Digidol (DOIs)	https://doi.org/10.1016/j.cell.2022.07.002
Statws	Cyhoeddwyd - 4 Awst 2022
Cyhoeddwyd yn allanol	Ie

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10.1016/j.cell.2022.07.002Trwydded: CC BY

Version of Record with a CC BY LicenceFersiwn derfynol wedi’i chyhoeddi, 9.56 MBTrwydded: CC BY

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Dolton, G., Rius, C., Hasan, M. S., Wall, A., Szomolay, B., Behiry, E., Whalley, T., Southgate, J., Fuller, A., COVID-19 Genomics UK (COG-UK) consortium, 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. (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{882723d377874137b078a5e240050f07,

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 = "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 {COVID-19 Genomics UK (COG-UK) consortium} 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}",

year = "2022",

month = aug,

day = "4",

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

language = "English",

volume = "185",

pages = "2936--2951.e19",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "16",

}

Dolton, G, Rius, C, Hasan, MS, Wall, A, Szomolay, B, Behiry, E, Whalley, T, Southgate, J, Fuller, A, COVID-19 Genomics UK (COG-UK) consortium, Morin, T, Topley, K, Tan, LR, Goulder, PJR, Spiller, OB, Rizkallah, PJ, Jones, LC, Connor, TR & Sewell, AK 2022, 'Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope', Cell, cyfrol. 185, rhif 16, tt. 2936-2951.e19. https://doi.org/10.1016/j.cell.2022.07.002

TY - JOUR

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

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

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

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

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 -

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

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