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

Abstract

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 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.

SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

“…In the context of SARS-CoV-2, Poran et al point out the potential of leveraging proteomic data to infer relative viral protein abundance (Poran et al, 2020b(Poran et al, , 2020a. Several other studies have eluted SARS-CoV-2-derived peptides bound to HLA (Knierman et al, 2020;Parker et al, 2020;Weingarten-Gabbay et al, 2020) but have not shown that the epitopes are actually recognized by T cell responses. Future studies will examine the correspondence between eluted ligands and T cell recognition.…”

“…In addition, the results of the IEDB curation were manually inspected by the coauthors to guard against papers missed by the IEDB curation workflow, but no additional papers were identified. This review focuses on SARS-CoV-2 epitopes recognized by human T cells, and thus does not discuss related topics, such as studies identifying T cell epitopes recognized in murine systems (Hassert et al, 2020;Takagi and Matsui, 2021), studies characterizing SARS-CoV-2 peptides eluted from HLA molecules (Knierman et al, 2020;Parker et al, 2020, Weingarten-Gabbay et al, 2020, or characterized by HLA binding in the absence of T cell recognition data (Prachar et al, 2020).…”

Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

“…In contrast to neutralizing antibody epitopes, T cell epitopes are located along the full length of the spike protein and T cell responses are broadly targeted in natural infection (22,(26)(27)(28)(29). Thus, it is unsurprising that the B.…”

MS-Based HLA-II Peptidomics Combined With Multiomics Will Aid the Development of Future Immunotherapies

“…Investigations into the role of HLA-II in immune responses in the context of infectious disease are important for understanding disease pathology and the development of potential treatments. To date, susceptibility to Hepatitis B, Dengue, and West Nile Virus has been associated with specific HLA-II alleles 45,74,75 and CD4+ T cell responses have been documented in a range of infectious diseases, including Chikungunya, Tuberculosis, and COVID-19 [76][77][78][79] . Moreover, many viruses successfully evade the immune system by altering HLA-II expression.…”