tetano
Editor, Senior Moderator
Cell Rep
. 2021 May 13;109179.
doi: 10.1016/j.celrep.2021.109179. Online ahead of print.
Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells
Robert Parker[SUP] 1 [/SUP], Thomas Partridge[SUP] 2 [/SUP], Catherine Wormald[SUP] 2 [/SUP], Rebeca Kawahara[SUP] 3 [/SUP], Victoria Stalls[SUP] 4 [/SUP], Maria Aggelakopoulou[SUP] 2 [/SUP], Jimmy Parker[SUP] 5 [/SUP], Rebecca Powell Doherty[SUP] 6 [/SUP], Yoanna Ariosa Morejon[SUP] 7 [/SUP], Esther Lee[SUP] 4 [/SUP], Kevin Saunders[SUP] 4 [/SUP], Barton F Haynes[SUP] 4 [/SUP], Priyamvada Acharya[SUP] 8 [/SUP], Morten Thaysen-Andersen[SUP] 9 [/SUP], Persephone Borrow[SUP] 10 [/SUP], Nicola Ternette[SUP] 11 [/SUP]
Affiliations
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 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[SUP]+[/SUP] T cell responses in infected individuals and vaccine recipients and have application in next-generation vaccine design.
Keywords: HLA class II; HLA-II; LC-MS; SARS-CoV-2; antigen presentation; dentritic cells; glycopeptides; glycoslyation; human leukocyte antigen; immunopeptidomics.
. 2021 May 13;109179.
doi: 10.1016/j.celrep.2021.109179. Online ahead of print.
Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells
Robert Parker[SUP] 1 [/SUP], Thomas Partridge[SUP] 2 [/SUP], Catherine Wormald[SUP] 2 [/SUP], Rebeca Kawahara[SUP] 3 [/SUP], Victoria Stalls[SUP] 4 [/SUP], Maria Aggelakopoulou[SUP] 2 [/SUP], Jimmy Parker[SUP] 5 [/SUP], Rebecca Powell Doherty[SUP] 6 [/SUP], Yoanna Ariosa Morejon[SUP] 7 [/SUP], Esther Lee[SUP] 4 [/SUP], Kevin Saunders[SUP] 4 [/SUP], Barton F Haynes[SUP] 4 [/SUP], Priyamvada Acharya[SUP] 8 [/SUP], Morten Thaysen-Andersen[SUP] 9 [/SUP], Persephone Borrow[SUP] 10 [/SUP], Nicola Ternette[SUP] 11 [/SUP]
Affiliations
- PMID: 34004174
- DOI: 10.1016/j.celrep.2021.109179
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 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[SUP]+[/SUP] T cell responses in infected individuals and vaccine recipients and have application in next-generation vaccine design.
Keywords: HLA class II; HLA-II; LC-MS; SARS-CoV-2; antigen presentation; dentritic cells; glycopeptides; glycoslyation; human leukocyte antigen; immunopeptidomics.