Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells
| Autor: | Rebecca Powell Doherty, Persephone Borrow, Morten Thaysen-Andersen, Kevin O. Saunders, Yoanna Ariosa Morejon, Rebeca Kawahara, Robert Parker, Maria Aggelakopoulou, Barton F. Haynes, Thomas Partridge, Jimmy Parker, Esther Lee, Priyamvada Acharya, Nicola Ternette, Victoria Stalls, Catherine Wormald |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Glycan Glycosylation T-Lymphocytes T cell Antigen presentation Epitopes T-Lymphocyte Peptide Human leukocyte antigen General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system medicine Humans Protein Interaction Domains and Motifs Amino Acid Sequence Peptide sequence chemistry.chemical_classification Antigen Presentation biology SARS-CoV-2 Antigen processing Repertoire Histocompatibility Antigens Class II COVID-19 Dendritic Cells Virology 030104 developmental biology Epitope mapping medicine.anatomical_structure chemistry Spike Glycoprotein Coronavirus biology.protein Peptides Glycoprotein 030217 neurology & neurosurgery Epitope Mapping Protein Binding |
| Zdroj: | bioRxiv Cell Reports |
| DOI: | 10.1101/2020.08.19.255901 |
| Popis: | 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. Graphical Abstract Parker et al map the HLA-II-bound peptides and glycopeptides presented by SARS-Cov-2 spike protein-pulsed monocyte-derived dendritic cells. They observe that complex glycans on the spike immunogen are trimmed during antigen processing, revealing a signature for HLA-II presentation, and highlight congruence between the HLA-II-bound peptides identified and T cell epitopes. |
| Databáze: | OpenAIRE |
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