CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens.

Détails

ID Serval
serval:BIB_848F6AADEDBE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens.
Périodique
Molecular & cellular proteomics
Auteur(s)
Forlani G., Michaux J., Pak H., Huber F., Marie Joseph E.L., Ramia E., Stevenson B.J., Linnebacher M., Accolla R.S., Bassani-Sternberg M.
ISSN
1535-9484 (Electronic)
ISSN-L
1535-9476
Statut éditorial
Publié
Date de publication
06/01/2021
Peer-reviewed
Oui
Volume
20
Pages
100032
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Résumé
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.
Mots-clé
Analytical Chemistry, Biochemistry, Molecular Biology, Antigen discovery, Class II major histocompatibility complex transactivator, Glioblastoma, Immunopeptidomics
Pubmed
Web of science
Open Access
Oui
Financement(s)
Conseil Européen de la Recherche (ERC)
Création de la notice
09/10/2020 7:59
Dernière modification de la notice
05/06/2021 5:33
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