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Regulation of HLA II expression in acute myeloid leukemia by CIITA methylation (RNA-seq dataset)

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

PROVIDER: PRJNA631929 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11777200_1.fastq.gz	Fastqsanger.gz
	SRR11777200_2.fastq.gz	Fastqsanger.gz
	SRR11777201_1.fastq.gz	Fastqsanger.gz
	SRR11777201_2.fastq.gz	Fastqsanger.gz
	SRR11777202_1.fastq.gz	Fastqsanger.gz

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Regulation of HLA II expression in acute myeloid leukemia by CIITA methylation (RNA-seq dataset)

Project description:Acute myeloid leukemia cell lines were treated with the hypomethylating agent decitabine and interferon gamma to investigate if these treatments induce HLA II gene expression. Cells carrying either control or CIITA-targeting sgRNAs were used to test the dependence of the HLA II induction on CIITA.

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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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CIITA

Project description:CIITA

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Regulation of HLA II expression in acute myeloid leukemia by CIITA methylation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-13 | GSE150374 | GEO

HLA-DR is absent in primitive macrophages through epigenetic silencing of master regulator CIITA

Project description:The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.

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CIITA

Project description:Creation of comprehensive CIITA and RFX5 ChIP-Seq profiles in primary B cells and monocytes

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