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Regulation of HLA II expression in acute myeloid leukemia by CIITA methylation (RRBS dataset)

ABSTRACT: Regulation of HLA II expression in acute myeloid leukemia by CIITA methylation (RRBS dataset)

PROVIDER: PRJNA631928 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11777119_1.fastq.gz	Fastqsanger.gz
	SRR11777119_2.fastq.gz	Fastqsanger.gz
	SRR11777120_1.fastq.gz	Fastqsanger.gz
	SRR11777120_2.fastq.gz	Fastqsanger.gz
	SRR11777121_1.fastq.gz	Fastqsanger.gz

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Regulation of HLA II expression in acute myeloid leukemia by CIITA methylation (RRBS dataset)

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CIITA-transduced glioblastoma cells uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens

Project description:CD4+ T cell responses are crucial for inducing and maintaining effective anti-cancer immunity, and the identification of 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 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 to 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 such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire.

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