ArticleMolecular & cellular proteomics : MCP2012
Major histocompatibility complex class II+ invariant chain negative breast cancer cells present unique peptides that activate tumor-specific T cells from breast cancer patients.
Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- The aryl hydrocarbon receptor (AHR) drives human leukocyte antigen (HLA)-II expression in human melanoma.Journal of experimental & clinical cancer research : CR · 2026Article
- What do cancer-specific T cells 'see'?Discovery immunology · 2023Review
- Article
- Citrullinated Epitopes Identified on Tumour MHC Class II by Peptide Elution Stimulate Both Regulatory and Th1 Responses and Require Careful Selection for Optimal Anti-Tumour Responses.Frontiers in immunology · 2021Article
- Review
- The Role of Mass Spectrometry and Proteogenomics in the Advancement of HLA Epitope Prediction.Proteomics · 2018Review
- MHC class II associated stomach cancer mutations correlate with lack of subsequent tumor development.Molecular and clinical oncology · 2017Article
- Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy.Oncotarget · 2017Article
- CD74 and intratumoral immune response in breast cancer.Oncotarget · 2017Article
- Sampling From the Proteome to the Human Leukocyte Antigen-DR (HLA-DR) Ligandome Proceeds Via High Specificity.Molecular & cellular proteomics : MCP · 2016Article
- Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy.Nature communications · 2016Article
- Novel strategies for inhibiting PD-1 pathway-mediated immune suppression while simultaneously delivering activating signals to tumor-reactive T cells.Cancer immunology, immunotherapy : CII · 2015Review
- Elevation of c-MYC disrupts HLA class II-mediated immune recognition of human B cell tumors.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Endogenous Antigen Presentation of MHC Class II Epitopes through Non-Autophagic Pathways.Frontiers in immunology · 2015Review
- Exposing the Specific Roles of the Invariant Chain Isoforms in Shaping the MHC Class II Peptidome.Frontiers in immunology · 2013Review
- The human leukocyte antigen-presented ligandome of B lymphocytes.Molecular & cellular proteomics : MCP · 2013Article
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4 authors.
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Abstract
The major histocompatibility complex (MHC) class II-associated Invariant chain (Ii) is present in professional antigen presenting cells where it regulates peptide loading onto MHC class II molecules and the peptidome presented to CD4+ T lymphocytes. Because Ii prevents peptide loading in neutral subcellular compartments, we reasoned that Ii- cells may present peptides not presented by Ii+ cells. Based on the hypothesis that patients are tolerant to MHC II-restricted tumor peptides presented by Ii+ cells, but will not be tolerant to novel peptides presented by Ii- cells, we generated MHC II vaccines to activate cancer patients' T cells. The vaccines are Ii- tumor cells expressing syngeneic HLA-DR and the costimulatory molecule CD80. We used liquid chromatography coupled with mass spectrometry to sequence MHC II-restricted peptides from Ii+ and Ii- MCF10 human breast cancer cells transfected with HLA-DR7 or the MHC Class II transactivator CIITA to determine if Ii- cells present novel peptides. Ii expression was induced in the HLA-DR7 transfectants by transfection of Ii, and inhibited in the CIITA transfectants by RNA interference. Peptides were analyzed and binding affinity predicted by artificial neural net analysis. HLA-DR7-restricted peptides from Ii- and Ii+ cells do not differ in size or in subcellular location of their source proteins; however, a subset of HLA-DR7-restricted peptides of Ii- cells are not presented by Ii+ cells, and are derived from source proteins not used by Ii+ cells. Peptides from Ii- cells with the highest predicted HLA-DR7 binding affinity were synthesized, and activated tumor-specific HLA-DR7+ human T cells from healthy donors and breast cancer patients, demonstrating that the MS-identified peptides are bonafide tumor antigens. These results demonstrate that Ii regulates the repertoire of tumor peptides presented by MHC class II+ breast cancer cells and identify novel immunogenic MHC II-restricted peptides that are potential therapeutic reagents for cancer patients.
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