| Reference | ||
|---|---|---|
| Reference Type | Literature | IEDB_Reference:1040330 |
| Title | IFNγ Modulates the Immunopeptidome of Triple Negative Breast Cancer Cells by Enhancing and Diversifying Antigen Processing and Presentation. | |
| Authors | Gabriel Goncalves; Kerry A Mullan; Divya Duscharla; Rochelle Ayala; Nathan P Croft; Pouya Faridi; Anthony W Purcell | |
| Affiliations | Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia. | |
| Journal | Front Immunol | |
| Year | 2021 | |
| Abstract | Peptide vaccination remains a viable approach to induce T-cell mediated killing of tumors. To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon- (IFN) on the transcriptome, proteome, and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFN resulted in a remarkable remolding of the immunopeptidome, with only a 34% overlap between untreated and treated cells across the HLA-I immunopeptidome, and expression of HLA-II only detected on treated cells. IFN increased the overall number, diversity, and abundance of peptides contained within the immunopeptidome, as well increasing the coverage of individual source antigens. The suite of peptides displayed under conditions of IFN treatment included many known tumor associated antigens, with the HLA-II repertoire sampling 17 breast cancer associated antigens absent from those sampled by HLA-I molecules. Quantitative analysis of the transcriptome (10,248 transcripts) and proteome (6,783 proteins) of these cells revealed 229 common proteins and transcripts that were differentially expressed. Most of these represented downstream targets of IFN signaling including components of the antigen processing machinery such as tapasin and HLA molecules. However, these changes in protein expression did not explain the dramatic modulation of the immunopeptidome following IFN treatment. These results demonstrate the high degree of plasticity in the immunopeptidome of TNBC cells following cytokine stimulation and provide evidence that under pro-inflammatory conditions a greater variety of potential HLA-I and HLA-II vaccine targets are unveiled to the immune system. This has important implications for the development of personalized cancer vaccination strategies. | |
| External Link | PXD023044 | |
| External Link | PXD023038 | |
| Curation Last Updated | 2024-09-17 02:47:46 | |
| Epitope | ||
|---|---|---|
| Epitope ID | 1900791 | IEDB_epitope:1900791 |
| Chemical Type | Linear peptide | |
| Linear Sequence | IRNVPYRIRVRLSRKRNED | |
| Source Molecule Name | 60S ribosomal protein L31 | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 77 | |
| Ending Position | 95 | |
| Epitope Reference Details | ||
|---|---|---|
| Epitope Structure Defines | Epitope containing region/antigenic site | |
| Epitope Name | Eluted Peptide 75763 | |
| Location of Data in Reference | Author Provided | |
| In Vivo Processing | ||
|---|---|---|
| Host Organism | Homo sapiens (human) | |
| Host Details | ||
|---|---|---|
| MHC Types present | HLA-DPB1*02:01;HLA-DPB1*17:01;HLA-DQB1*02:02;HLA-DQB1*03:01;HLA-DRB1*07:01;HLA-DRB1*13:05 | |
| In Vivo Process | ||
|---|---|---|
| In Vivo Process Type | Occurrence of cancer | |
| Disease State | breast adenocarcinoma | |
| Disease Stage | Unknown; | |
| Antigen Processing Comments | ||
|---|---|---|
| Antigen Processing Comments | MDA-MB-231 cells were treated with IFNg then subjected to MHC ligand elution. | |
| MHC Ligand Assay | ||
|---|---|---|
| Qualitative Measurement | Positive | |
| Method/Technique | cellular MHC/mass spectrometry | |
| Measurement of | ligand presentation | |
| Antigen Presenting Cells | ||
|---|---|---|
| Cell Tissue Type | Lymphoid | |
| Cell Type | MDA-MB-231-Epithelial cell | http://purl.obolibrary.org/obo/CLO_0007634 |
| Cell Culture Conditions | Cell Line / Clone | |
| MHC Allele | ||
|---|---|---|
| MHC Allele Name | HLA class II | |
| MHC Evidence Code | Elution with MHC specific antibody | |
| MHC Ligand | ||
|---|---|---|
| Epitope Relation | Epitope | |
| Chemical Type | Linear peptide | |
| Linear Sequence | IRNVPYRIRVRLSRKRNED | |
| Source Molecule Name | 60S ribosomal protein L31 | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 77 | |
| Ending Position | 95 | |
| Assay Reference Details | ||
|---|---|---|
| Assay Comments by IEDB Curator | The epitope was eluted with a combination of the HLA class II allele-specific antibodies LB3.1 (HLA-DR), B721 (HLA-DP), and SPV-L3 (HLA DQ). | |
| Location of Assay Data in Reference | Author Provided | |