CIITA-transduced glioblastoma cells uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens
| العنوان: | CIITA-transduced glioblastoma cells uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens |
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| المؤلفون: | Michal Bassani-Sternberg, Elise Ramia, Brian Stevenson, Greta Forlani, Elodie Lauret Marie Joseph, Michael Linnebacher, Roberto S. Accolla, Florian Huber, HuiSong Pak, Justine Michaux |
| المصدر: | Molecular & Cellular Proteomics : MCP Molecular & cellular proteomics, vol. 20, pp. 100032 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Antigen discovery, CIITA, Cancer Biology, Cancer therapeutics, Glioblastoma, HLA class II, Immunology, Immunopeptidomics, Mass Spectrometry, Tumor antigens, HLA-II, human leukocyte antigen class II, Biochemistry, Epitope, WES, whole-exome sequencing, Analytical Chemistry, APCs, antigen presenting cells, 0303 health sciences, biology, Brain Neoplasms, 030302 biochemistry & molecular biology, a.u., arbitrary units, Nuclear Proteins, TH, T helper cells, 3. Good health, TAAs, tumor-associated antigens, medicine.anatomical_structure, SNPs, single nucleotide polymorphisms, PSM, peptide spectrum match, HLA-I, human leukocyte antigen class I, FDR, false discovery rate, T cell, Class II major histocompatibility complex transactivator, Human leukocyte antigen, Major histocompatibility complex, TcR, T cell receptors, IFNγ, Interferon gamma, ER, endoplasmic reticulum, 03 medical and health sciences, Antigen, Special Issue: Immunopeptidomics, ERAAP, ER aminopeptidase-associated with antigen processing, Antigens, Neoplasm, Cell Line, Tumor, medicine, MHC, major histocompatibility complex, Animals, Humans, Antigen-presenting cell, Molecular Biology, 030304 developmental biology, PBMCs, peripheral blood mononuclear cells, HLA, human leukocyte antigen, Research, T-cell receptor, Histocompatibility Antigens Class II, LFQ, label-free quantification, TAP, transporter-associated with antigen processing, CTL, cytotoxic T cells, CIITA, class II major histocompatibility complex transactivator, HCD, higher-energy collision dissociation, biology.protein, Cancer research, Trans-Activators, Antigens, Neoplasm/immunology, Brain Neoplasms/immunology, Cattle, Glioblastoma/immunology, Histocompatibility Antigens Class II/immunology, Nuclear Proteins/genetics, Nuclear Proteins/immunology, Peptides/immunology, Trans-Activators/genetics, Trans-Activators/immunology, GBM, glioblastoma, Peptides, SNVs, single nucleotide variants |
| الوصف: | CD4+ T cell responses are crucial for inducing and maintaining effective anticancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry–based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17, and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared with interferon gamma (IFNɣ) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire. Graphical Abstract Highlights • CIITA-expressing glioblastoma cells express high levels of HLA-II complexes. • CIITA induces peptide presentation across the HLA-DP, -DQ, and -DR allotypes. • Many clinically relevant glioblastoma-associated tumor antigens were detected. • Such cells may have great therapeutic potential in clinical settings. In Brief CD4+ T cell responses are crucial for inducing and maintaining effective anticancer immunity; however, in glioblastoma and many solid tumors, HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in glioblastoma. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed immunopeptidomics, we uncovered a remarkable breadth of the HLA-ligandome in three glioblastoma cell lines and identified many cancer-associated ligands with implications for the development of cancer immunotherapies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfcddca7fc19ba47138689bfadc4b41eTest http://hdl.handle.net/11383/2103085Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bfcddca7fc19ba47138689bfadc4b41e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |