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Pre-Existing Cellular Immunity to SARS-CoV-2 Through an Immunodominant Epitope

56 Pages Posted: 27 Jan 2021 Publication Status: Published

See all articles by Katie E. Lineburg

Katie E. Lineburg

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Emma J. Grant

Monash University - Department of Biochemistry and Molecular Biology

Srividhya Swaminathan

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Demetra S.M. Chatzileontiadou

La Trobe University - Department of Biochemistry & Chemistry

Christopher Szeto

Monash University - Department of Biochemistry and Molecular Biology

Hannah Sloane

Monash University - Department of Biochemistry and Molecular Biology

Archana Panikkar

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Jyothy Raju

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Pauline Crooks

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Sweera Rehan

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Andrea Nguyen

Monash University - Department of Biochemistry and Molecular Biology

Lea Lekieffre

QIMR Berghofer Medical Research Institute - Infectious Diseases Programme

Michelle A. Neller

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Zhen Wei Marcus Tong

University of Queensland - School of Chemistry & Molecular Biosciences

Dhilshan Jayasinghe

Monash University - Department of Biochemistry and Molecular Biology

Keng Yih Chew

University of Queensland - School of Chemistry & Molecular Biosciences

Christian A. Lobos

Monash University - Department of Biochemistry and Molecular Biology

Hanim Halim

Monash University - Department of Biochemistry and Molecular Biology

Jacqueline M. Burrows

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Alan Riboldi-Tunnicliffe

ANSTO - Australian Synchrotron

Weisan Chen

La Trobe University - Department of Biochemistry and Genetics

Lloyd D'Orsogna

Fiona Stanley Hospital - Department of Clinical Immunology

Rajiv Khanna

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Kirsty R. Short

University of Queensland - School of Chemistry & Molecular Biosciences; University of Queensland - School of Public Health

Corey Smith

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Stephanie Gras

La Trobe University - Department of Biochemistry & Chemistry

More...

Abstract

Significant efforts are being made worldwide to understand the immune response to SARS-CoV-2, responsible for the COVID-19 pandemic, including the role of pre-existing T cell immunity. Understanding the mechanisms that promote cross-recognition by T cells induced by seasonal coronaviruses will be critical for future predictions on the role of pre-existing immunity in protection against severe disease. We demonstrate that the SARS-CoV-2 nucleocapsid (N) protein induces an immunodominant response in HLA-B7+ COVID-19-recovered individuals that is also readily detectable in unexposed donors. This immunodominant response is driven by a single N-encoded epitope that displays a high degree of conservation with the homologous region in circulating coronaviruses. We show that T cell-mediated cross-reactivity can be detected towards the circulating OC43/HKU-1 coronaviruses, but not the 229E or NL63 coronaviruses, due to different peptide conformations. This cross-reactivity is driven by private T cell receptor repertoires with a bias for TRBV27 and a long CDR3b loop in unexposed and COVID-19-recovered individuals. Together, our findings demonstrate the basis of pre-existing immunity to a conserved and highly immunogenic SARS-CoV-2 epitope driven by cross-reactive memory T cells, suggesting long-lived protective immunity.

Funding: This work was supported by generous donations from the QIMR Berghofer COVID 19 appeal, and financial contributions from Monash University, Australian Nuclear Science and Technology Organisation (ANSTO, AISNE ECR grants), Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), and the Medical Research Future Fund (MRFF). H.S. is supported by an Australian Government Research Training Program Scholarship, E.J.G. was supported by an NHMRC CJ Martin Fellowship (#1110429) and is supported by an Australian Research Council DECRA (DE210101479), K.R.S.is supported by an Australian Research Council DECRA (DE180100512), S.G. is supported by and NHMRC SRF (#1159272).

Conflict of Interest: The authors declare no competing interests.

Ethical Approval: This study was performed according to the principles of the Declaration of Helsinki.Ethics approval to undertake the research was obtained from the QIMR Berghofer Medical Research Institute Human Research Ethics Committee and Monash University Human Research Ethics Committee.

Suggested Citation

Lineburg, Katie E. and Grant, Emma J. and Swaminathan, Srividhya and Chatzileontiadou, Demetra S.M. and Szeto, Christopher and Sloane, Hannah and Panikkar, Archana and Raju, Jyothy and Crooks, Pauline and Rehan, Sweera and Nguyen, Andrea and Lekieffre, Lea and Neller, Michelle A. and Tong, Zhen Wei Marcus and Jayasinghe, Dhilshan and Chew, Keng Yih and Lobos, Christian A. and Halim, Hanim and Burrows, Jacqueline M. and Riboldi-Tunnicliffe, Alan and Chen, Weisan and D'Orsogna, Lloyd and Khanna, Rajiv and Short, Kirsty R. and Smith, Corey and Gras, Stephanie, Pre-Existing Cellular Immunity to SARS-CoV-2 Through an Immunodominant Epitope. Available at SSRN: https://ssrn.com/abstract=3774361 or http://dx.doi.org/10.2139/ssrn.3774361
This version of the paper has not been formally peer reviewed.

Katie E. Lineburg

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Emma J. Grant

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Srividhya Swaminathan

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Demetra S.M. Chatzileontiadou

La Trobe University - Department of Biochemistry & Chemistry ( email )

Christopher Szeto

Monash University - Department of Biochemistry and Molecular Biology

Clayton, Victoria
Australia

Hannah Sloane

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Archana Panikkar

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Jyothy Raju

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Pauline Crooks

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Sweera Rehan

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Andrea Nguyen

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Lea Lekieffre

QIMR Berghofer Medical Research Institute - Infectious Diseases Programme

Brisbane, Queensland
Australia

Michelle A. Neller

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Zhen Wei Marcus Tong

University of Queensland - School of Chemistry & Molecular Biosciences ( email )

St. Lucia
Brisbane
Australia

Dhilshan Jayasinghe

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Keng Yih Chew

University of Queensland - School of Chemistry & Molecular Biosciences

St. Lucia
Brisbane
Australia

Christian A. Lobos

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Hanim Halim

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Jacqueline M. Burrows

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Alan Riboldi-Tunnicliffe

ANSTO - Australian Synchrotron ( email )

Weisan Chen

La Trobe University - Department of Biochemistry and Genetics

Department of Economics and Finance
Victoria 3552, 3086
Australia

Lloyd D'Orsogna

Fiona Stanley Hospital - Department of Clinical Immunology

Australia

Rajiv Khanna

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development

Australia

Kirsty R. Short

University of Queensland - School of Chemistry & Molecular Biosciences ( email )

St. Lucia
Brisbane
Australia

University of Queensland - School of Public Health ( email )

St Lucia
Brisbane
Australia

Corey Smith

QIMR Berghofer Medical Research Institute - QIMR Berghofer Centre for Immunotherapy and Vaccine Development ( email )

Australia

Stephanie Gras (Contact Author)

La Trobe University - Department of Biochemistry & Chemistry ( email )

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