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Mapping naturally presented T-cell antigens in medulloblastoma based on integrative multi-omics

ABSTRACT: Mapping naturally presented T-cell antigens in medulloblastoma based on integrative multi-omics

PROVIDER: PRJNA1054577 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25412800_1.fastq.gz	Fastqsanger.gz
	SRR25412800_2.fastq.gz	Fastqsanger.gz
	SRR25412801_1.fastq.gz	Fastqsanger.gz
	SRR25412801_2.fastq.gz	Fastqsanger.gz
	SRR25412802_1.fastq.gz	Fastqsanger.gz

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Mapping naturally presented T-cell antigens in medulloblastoma based on integrative multi-omics [RNA-seq]

Project description:Medulloblastoma is the most frequent malignant primary brain tumor in children. Despite recent advances in integrated genomics, the prognosis in children with high-risk medulloblastoma remains devastating, and new tumor-specific therapeutic approaches are needed. Here, we present an atlas of naturally presented T-cell antigens in medulloblastoma. We mapped the human leukocyte antigen (HLA)-presented peptidomes of 28 tumors and performed comparative immunopeptidome profiling against an in-house benign database. Medulloblastoma proved to be a rich source of novel tumor-associated antigens, naturally presented on HLA class I and II molecules. Remarkably, most tumor-associated peptides and proteins were subgroup-specific, whereas shared presentation among all subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) was rare. Functional testing of top-ranking novel candidate antigens demonstrated the induction of peptide-specific T-cell responses, supporting their potential for T-cell immunotherapy. This study is an in-depth mapping of naturally presented T-cell antigens in medulloblastoma. Integration of immunopeptidomics, transcriptomics, and epigenetic data led to the identification of a large set of actionable targets that can be further used for the translation into the clinical setting by facilitating the informed design of immunotherapeutic approaches to children with medulloblastoma.

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Identification of antigens presented by MHC for vaccines against tuberculosis

Project description:The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. We have purified MHC class-I and MHC-II peptides and analysed them by mass spectrometry. We have successfully identified 97 mycobacterial peptides presented by MHC-II and 54 presented by MHC-I, from 76 and 41 antigens, respectively. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cells from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying novel candidate antigens.

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