Summary 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 Highlights • DC-presented HLA-II-bound peptidome of SARS-CoV-2 spike glycoprotein • Spike glycans are truncated during glycopeptide processing and presentation • The spike receptor binding motif is a HLA-II-binding peptide-rich region • Concordance between the immunopeptidome and T cell immunogenicity data reported elsewhere 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.
【저자키워드】 SARS-CoV-2, human leukocyte antigen, Antigen presentation, LC-MS, HLA-II, HLA class II, dentritic cells, immunopeptidomics, glycoslyation, glycopeptides, 【초록키워드】 Vaccine, coronavirus, glycosylation, spike, Vaccine design, peptide, CD4, dendritic cells, Antigen, Protein, Epitopes, SARS-CoV-2 spike glycoprotein, response, understanding, receptor-binding motif, receptor binding motif, HLA-DR, dendritic cell, glycan, SARS-CoV-2 spike, Analysis, leukocyte, acute respiratory syndrome, Abstract, infected individual, protective immune response, residue, immunogenicity data, antigen processing, recipient, regions, responses, highlight, observé, Result, identify, reported, facilitate, unique, the S protein, cross-protective, reveal, glycosylated, complex glycan, 【제목키워드】 dendritic cell, mapping, the SARS-CoV-2,