Abstract
SummaryUnderstanding 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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel beta-coronavirus that first emerged as a human pathogen in the Hubei province of China in late 2019 and is the etiologic agent of coronavirus disease 2019 (COVID-19)
Approach for analysis of SARS-CoV-2 S human leukocyte antigen class II (HLA-II) presentation by monocyte-derived DCs (MDDCs) To identify peptides in the SARS-CoV-2 S protein with potential for targeting by CD4+ T cell responses, a mass-spectrometrybased immunopeptidome profiling approach was employed to define peptides presented by human leukocyte antigen (HLA)-II on dendritic cells (DCs), antigen presenting cells that play a key role in in vivo CD4+ T cell priming (Figure 1A)
MDDCs were generated from 5 HLA-DRB1-heterozygous donors, selected to enable profiling of peptides presented with a total of 9 different HLA-DRB1 alleles, 5 different HLA-DRB3/4/5 alleles, and 7 distinct HLA-DPB1 alleles (Table 1)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel beta-coronavirus that first emerged as a human pathogen in the Hubei province of China in late 2019 and is the etiologic agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection is frequently asymptomatic or results in only mild illness, $20% of symptomatically infected individuals progress to develop severe pneumonia, acute respiratory distress syndrome, and/or sepsis, which can be fatal. Transferred neutralizing antibodies (nAbs) protect against SARS-CoV-2 infection in small animal models, and convalescent sera have been shown to be effective in the treatment of severe disease, suggesting the utility of nAb induction by vaccines (Brouwer et al, 2020; Zost et al, 2020; Liu et al, 2020). The four seasonal common cold-causing human coronaviruses, the zoonotic Middle East respiratory syndrome (MERS), and SARS coronaviruses typically elicit poorly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
