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HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses

View ORCID ProfilePaul R. Buckley, View ORCID ProfileChloe H. Lee, View ORCID ProfileMariana Pereira Pinho, Rosana Ottakandathil Babu, Jeongmin Woo, View ORCID ProfileAgne Antanaviciute, View ORCID ProfileAlison Simmons, View ORCID ProfileGraham Ogg, View ORCID ProfileHashem Koohy
doi: https://doi.org/10.1101/2021.07.17.452778
Paul R. Buckley
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
2MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Chloe H. Lee
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
2MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Mariana Pereira Pinho
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Rosana Ottakandathil Babu
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
2MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Jeongmin Woo
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
2MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Agne Antanaviciute
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
2MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Alison Simmons
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Graham Ogg
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Hashem Koohy
1MRC Human Immunology Unit, Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
2MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  • For correspondence: hashem.koohy@rdm.ox.ac.uk
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Abstract

Pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure to SARS-CoV-2 has been reported in several studies. While emerging evidence hints toward prior exposure to common-cold human coronaviruses (HCoV), the extent of- and conditions for-cross-protective immunity between SARS-CoV-2 and HCoVs remain open. Here, by leveraging a comprehensive pool of publicly available functionally evaluated SARS-CoV-2 peptides, we report 126 immunogenic SARS-CoV-2 peptides with high sequence similarity to 285 MHC-presented target peptides from at least one of four HCoV, thus providing a map describing the landscape of SARS-CoV-2 shared and private immunogenic peptides with functionally validated T cell responses. Using this map, we show that while SARS-CoV-2 immunogenic peptides in general exhibit higher level of dissimilarity to both self-proteome and -microbiomes, there exist several SARS-CoV-2 immunogenic peptides with high similarity to various human protein coding genes, some of which have been reported to have elevated expression in severe COVID-19 patients. We then combine our map with a SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls and show that whereas the public repertoire for the majority of convalescent patients are dominated by TCRs cognate to private SARS-CoV-2 peptides, for a subset of patients, more than 50% of their public repertoires that show reactivity to SARS-CoV-2, consist of TCRs cognate to shared SARS-CoV-2-HCoV peptides. Further analyses suggest that the skewed distribution of TCRs cognate to shared and private peptides in COVID-19 patients is likely to be HLA-dependent. Finally, by utilising the global prevalence of HLA alleles, we provide 10 peptides with known cognate TCRs that are conserved across SARS-CoV-2 and multiple human coronaviruses and are predicted to be recognised by a high proportion of the global population. Overall, our work indicates the potential for HCoV-SARS-CoV-2 reactive CD8+ T cells, which is likely dependent on differences in HLA-coding genes among individuals. These findings may have important implications for COVID-19 heterogeneity and vaccine-induced immune responses as well as robustness of immunity to SARS-CoV-2 and its variants.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 20, 2021.
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HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses
Paul R. Buckley, Chloe H. Lee, Mariana Pereira Pinho, Rosana Ottakandathil Babu, Jeongmin Woo, Agne Antanaviciute, Alison Simmons, Graham Ogg, Hashem Koohy
bioRxiv 2021.07.17.452778; doi: https://doi.org/10.1101/2021.07.17.452778
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HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses
Paul R. Buckley, Chloe H. Lee, Mariana Pereira Pinho, Rosana Ottakandathil Babu, Jeongmin Woo, Agne Antanaviciute, Alison Simmons, Graham Ogg, Hashem Koohy
bioRxiv 2021.07.17.452778; doi: https://doi.org/10.1101/2021.07.17.452778

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