Identification and Characterization of Complex Glycosylated Peptides Presented by the MHC Class II Processing Pathway in Melanoma

Malaker, Stacy A.; Ferracane, Michael J.; Depontieu, Florence; Zarling, Angela L.; Shabanowitz, Jeffrey; Bai, Dina L.; Topalian, Suzanne L.; Engelhard, Víctor H.; Hunt, Donald F.

doi:10.1021/acs.jproteome.6b00496

Cited by 40 publications

(39 citation statements)

References 36 publications

(72 reference statements)

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“…cathepsin D) are known to be abundantly expressed and highly active in MHC class II processing compartments (MIICs) 45 . Furthermore, MHC class II immunopeptides carrying truncated N-glycans have previously been reported from other cellular origins 46,47 . CD4+ T cell recognition of glycosylated peptides has been reported in rheumatoid arthritis (O-linked) 48 and cancer (N-linked) 49 , and CD4 + peptides in the melanoma antigen tyrosinase require the presence of N-linked glycosylation to elicit a T cell response 49 .…”

Section: Discussionmentioning

confidence: 99%

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

Parker

Partridge

Wormald

et al. 2020

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

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

Parker

Partridge

Wormald

et al. 2020

Preprint

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“…However, when that peptide contains a glycosylation site, the ability of the peptide to be presented in an HLA complex may be compromised, if for example the peptide cannot bind to the HLA molecule due to the steric presence of the glycan. However, glycopeptides may be presented in HLA complexes 73 if the glycan is small enough or if it is found on the end of the peptide antigen where it doesn't interfere with HLA binding 74 . The glycan-mediated shielding of predicted HLA antigens (Table S2) derived from the S protein are shown in Figures 4, S2 and S3 for all HLA peptide sequences that also contain a glycosite.…”

Section: Assessment Of the Impact Of Glycosylation On Antigenicitymentioning

confidence: 99%

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Grant

Montgomery

Ito

et al. 2020

Preprint

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Here we have generated 3D structures of glycoforms of the spike (S) protein SARS-CoV-2, based on reported 3D structures for the S protein and on reported glycomics data for the protein produced in HEK293 cells. We also report structures for glycoforms that represent those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi and ER), as well as those that are commonly observed on antigens present in other viruses.These models were subjected to MD simulation to take into account protein and glycan plasticity, and to determine the extent to which glycan microheterogeneity impacts antigenicity. Lastly, we have identified peptides in the S protein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine.

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“…Characteristics of antigen processing are currently not improving prediction of pMHC presentation. Recent progress is being made in developing more sensitive mass-spec-based analyses of MHC embedded peptide 32,124,125 . Such strategies, especially when combined with unbiased T cell analyses should significantly improve our ability to predict which peptides will be presented at the cell surface, capable of mounting an immune response.…”

Section: Epitope Mapping and Antigen Selection At A Genome-wide Levelmentioning

confidence: 99%

Determining T-cell specificity to understand and treat disease

Hadrup

Newell

2017

Nat Biomed Eng

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Identification and Characterization of Complex Glycosylated Peptides Presented by the MHC Class II Processing Pathway in Melanoma

Cited by 40 publications

References 36 publications

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

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

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Determining T-cell specificity to understand and treat disease

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