Dataset Information

Immunopeptidome analysis of 4T1 murine breast cancer cells.

ABSTRACT: This study aimed to identify Tumor Associated Antigens (TAA)s by Immunoaffinity purification of MHC peptides and LCMS analysis, verifying their immunogenicity and testing their tumor control potential in a highly aggressive preclinical model of triple-negative breast cancer in mice. Among the MHC peptides thus identified, an Endogenous Retroviral (ERV) peptide was also found, and this peptide, as well as several other peptides from TAAs, were shown to possess tumor control potential in a cancer vaccine setting in mice, by restricting tumor growth compared to controls.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Breast, Breast Cancer Cell Line, Breast Cancer Cell

DISEASE(S): Breast Cancer

SUBMITTER: Rui Branca

LAB HEAD: Janne Lehtiö

PROVIDER: PXD016112 | Pride | 2021-09-10

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Karita_Fusion_20180730exp_4T1_HLA-peptides_10of10ul.raw	Raw
	Karita_Fusion_20180801exp_4T1_HLA-peptides_10of10ul.raw	Raw
	Karita_Fusion_4T1_MHC-peptides_20190121_15cm-column_30min.raw	Raw
	Karita_Ligandome_Fusion_4T1_20180730_Byonic_reference-proteome.xlsx	Xlsx
	Karita_Ligandome_Fusion_4T1_20180730_Byonic_uniprot-mouse-sp-tr.xlsx	Xlsx

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Publications

Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy.

Peltonen Karita K Feola Sara S Umer Husen M HM Chiaro Jacopo J Mermelekas Georgios G Ylösmäki Erkko E Pesonen Sari S Branca Rui M M RMM Lehtiö Janne J Cerullo Vincenzo V

Cancers 20210707 14

Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interrogating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggressive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique antigens, among them a novel ERV ...[more]

PMID: 34298622

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Project description:Peptides displayed by MHC molecules on a cell’s surface, referred to as its immunopeptidome, play an important role in the adaptive the immune response. Antigen processing for MHC class I presentation is a ubiquitous pathway present in all nucleated cells which generate and present peptides of both self and non-self origin. Peptides with post-translational modifications (PTMs) are one of the classes of peptides presented by MHC class I molecules. However, due to the high background of self-peptides presented by the cells, the diversity of peptides with post-translational modifications is not well reported. In this study, we have carried out MHC Class I immunopeptidomics analysis on Jurkat and A375 cell lines to characterize the diversity of post-translational modifications among MHC class I peptides. Using high resolution mass spectrometry, we identified 25,761 MHC-bound peptides across both the cell lines using Bolt and Sequest search engines. High specificity of the enrichment method is demonstrated by identifying ~90% of the peptides with typical length distribution of 8-12 aa and enriched motifs within those peptides similar to the binding motifs of MHC alleles. Among the MHC-bound peptides, we identified phosphorylation as a major post-translational modification followed by deamidation. We observed site-specific localization of these post-translational modifications, at position P4 for phosphorylated peptides and position P3 for deamidated peptides. We identified a smaller number of peptides with acetylated and methylated lysine, possibly due to very low stoichiometric levels of these post-translational modifications compared to phosphorylation and deamidation. Using PEAKS de novo sequencing algorithm, we identified spliced peptides that account for ~5-7% of MHC-bound peptides across the two cell lines. These peptides share similar features with respect to normal MHC-bound peptides such as peptide length distribution and binding motifs. We validated the identification of several post-translationally modified peptides and spliced peptides using synthetic peptide sequences. In conclusion, our study demonstrates unbiased identification of these low stoichiometric PTMs and unusual spliced peptides using high resolution mass spectrometry.