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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)
18 Downloads (Pure)


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 profile 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 reveals substantial trimming of glycan residues on the latter, likely induced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region and identify S2-derived peptides with potential for targeting by cross-protective vaccine-elicited responses. Results from this study will aid analysis of CD4+ T cell responses in infected individuals and vaccine recipients and have application in next-generation vaccine design.

Original languageEnglish
Article number109179
Pages (from-to)1-16
Number of pages20
JournalCell Reports
Issue number8
Publication statusPublished - 25 May 2021

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • antigen presentation
  • dentritic cells
  • glycopeptides
  • glycoslyation
  • HLA class II
  • HLA-II
  • human leukocyte antigen
  • immunopeptidomics
  • LC-MS
  • SARS-CoV-2


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