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Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells

Robert Parker, Thomas Partridge, Catherine Wormald, Rebeca Kawahara, Victoria Stalls, Maria Aggelakopoulou, Jimmy Parker, Rebecca Powell Doherty, Yoanna Ariosa Morejon, Esther Lee, Kevin Saunders, Barton F. Haynes, Priyamvada Acharya, Morten Thaysen-Andersen, View ORCID ProfilePersephone Borrow, View ORCID ProfileNicola Ternette
doi: https://doi.org/10.1101/2020.08.19.255901
Robert Parker
1Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom
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  • For correspondence: robert.parker@ndm.ox.ac.uk nicola.ternette@ndm.ox.ac.uk persephone.borrow@ndm.ox.ac.uk
Thomas Partridge
2Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX37FZ, United Kingdom
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Catherine Wormald
2Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX37FZ, United Kingdom
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Rebeca Kawahara
3Department of Molecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia
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Victoria Stalls
4Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Maria Aggelakopoulou
2Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX37FZ, United Kingdom
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Jimmy Parker
6Wellbeing Software, Hamilton Court, Oakham Business Park, Mansfield, NG18 5FB, United Kingdom
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Rebecca Powell Doherty
1Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom
7Translational Gastroenterology Unit, Oxford, OX3 9DU, United Kingdom
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Yoanna Ariosa Morejon
1Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom
8The Kennedy Institute of Rheumatology, Oxford, OX3 7FY, United Kingdom
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Esther Lee
4Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Kevin Saunders
4Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Barton F. Haynes
4Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Priyamvada Acharya
4Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
5Department of Surgery, Duke University, Durham, NC 27710, USA
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Morten Thaysen-Andersen
3Department of Molecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia
9Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales 2109, Australia
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Persephone Borrow
2Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX37FZ, United Kingdom
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  • ORCID record for Persephone Borrow
  • For correspondence: robert.parker@ndm.ox.ac.uk nicola.ternette@ndm.ox.ac.uk persephone.borrow@ndm.ox.ac.uk
Nicola Ternette
1Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom
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  • ORCID record for Nicola Ternette
  • For correspondence: robert.parker@ndm.ox.ac.uk nicola.ternette@ndm.ox.ac.uk persephone.borrow@ndm.ox.ac.uk
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ABSTRACT

Understanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we have profiled the repertoire of human leukocyte antigen class II (HLA-II)-bound peptides presented by HLA-DR diverse monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike (S) protein. We identify 209 unique HLA-II-bound peptide sequences, many forming nested sets, which map to sites throughout S including glycosylated regions. Comparison of the glycosylation profile of the S protein to that of the HLA-II-bound S peptides revealed substantial trimming of glycan residues on the latter, likely introduced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region. Results from this study have application in vaccine design, and will aid analysis of CD4+ T cell responses in infected individuals and vaccine recipients.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 20, 2020.
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Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells
Robert Parker, Thomas Partridge, Catherine Wormald, Rebeca Kawahara, Victoria Stalls, Maria Aggelakopoulou, Jimmy Parker, Rebecca Powell Doherty, Yoanna Ariosa Morejon, Esther Lee, Kevin Saunders, Barton F. Haynes, Priyamvada Acharya, Morten Thaysen-Andersen, Persephone Borrow, Nicola Ternette
bioRxiv 2020.08.19.255901; doi: https://doi.org/10.1101/2020.08.19.255901
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Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells
Robert Parker, Thomas Partridge, Catherine Wormald, Rebeca Kawahara, Victoria Stalls, Maria Aggelakopoulou, Jimmy Parker, Rebecca Powell Doherty, Yoanna Ariosa Morejon, Esther Lee, Kevin Saunders, Barton F. Haynes, Priyamvada Acharya, Morten Thaysen-Andersen, Persephone Borrow, Nicola Ternette
bioRxiv 2020.08.19.255901; doi: https://doi.org/10.1101/2020.08.19.255901

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