Parker, RobertPartridge, ThomasWormald, CatherineKawahara, RebecaStalls, VictoriaAggelakopoulou, MariaParker, JimmyPowell Doherty, RebeccaAriosa Morejon, YoannaLee, EstherSaunders, KevinHaynes, Barton FAcharya, PriyamvadaThaysen-Andersen, MortenBorrow, PersephoneTernette, Nicola2021-06-012021-06-012021-05-132211-12472211-1247https://hdl.handle.net/10161/23226Understanding 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.HLA class IIHLA-IILC-MSSARS-CoV-2antigen presentationdentritic cellsglycopeptidesglycoslyationhuman leukocyte antigenimmunopeptidomicsJournal article2021-06-01