Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells.
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.
Parker, R; Partridge, T; Wormald, C; Kawahara, R; Stalls, V; Aggelakopoulou, M; Parker, J; Powell Doherty, R; Ariosa Morejon, Y; Lee, E; Saunders, K; Haynes, BF; Acharya, P; Thaysen-Andersen, M; Borrow, P; Ternette, N
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