Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells

Author:

Parker Robert,Partridge Thomas,Wormald Catherine,Kawahara Rebeca,Stalls Victoria,Aggelakopoulou Maria,Parker Jimmy,Doherty Rebecca Powell,Morejon Yoanna Ariosa,Lee Esther,Saunders Kevin,Haynes Barton F.,Acharya Priyamvada,Thaysen-Andersen Morten,Borrow PersephoneORCID,Ternette NicolaORCID

Abstract

ABSTRACTUnderstanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we have profiled 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 revealed substantial trimming of glycan residues on the latter, likely introduced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region. Results from this study have application in vaccine design, and will aid analysis of CD4+ T cell responses in infected individuals and vaccine recipients.

Publisher

Cold Spring Harbor Laboratory

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