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Induced pluripotent stem cells display a unique set of MHC I-associated peptides shared by cancer cells

ABSTRACT: We used a proteogenomic approach combining RNA-sequencing and mass spectrometry to study the MHC I-immunopeptidome specific to human iPSC samples. iPSCs were also analyzed after a 72h treatment with IFN-g (IFN-gamma) to boost MHC I levels and increase our chance for pluripotency-associated MHC I-associated peptide (paMAP) discovery. We identified 46 paMAPs which were absent from the RNA-seq of healthy somatic tissues and adult stem cells, but 40 of them were expressed in multiple cancer types from The Cancer Genome Atlas (TCGA). The antigens shared by iPSCs and tumors represent attractive targets for immunotherapy of poorly differentiated cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171226 | GEO | 2022/07/20

REPOSITORIES: GEO

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MHC II immunopeptidome during Plasmodium berghei blood stage infection

Project description:In malaria, T cells play a dual role by both restricting parasite growth and mediating immunopathology such as the deadly neuroinflammation called cerebral malaria. During experimental cerebral malaria (ECM), IFN produced by CD4 T cells promotes CD8 T cell sequestration in brain capillaries, resulting in endothelial damage, oedema and death. However the antigen-presenting cells controlling the development of CD4 T cell responses, as well as the antigens recognized by these CD4 T cells, are unknown. Here we used mass spectrometry to characterize the MHC II immunopeptidome presented by dendritic cells during blood stage malaria in C57BL/6 mice. We identified 14 MHC II ligands derived from 13 conserved Plasmodium berghei proteins that we validated in vivo. This work profiles the first MHC II immunopeptidome in a mouse model of blood stage malaria.

2017-09-20 | PXD007628 | Pride

Next Generation Sequencing of hormone receptor-positive and triple negative primary breast cancer tumors

Project description:In order to identify relevant targets for cancer immunotherapy in breast cancer, we characterized the immunopeptidome of 26 primary breast cancer samples with a proteogenomic approach relying on RNA-seq and mass spectrometry (MS). We were able to describe the landscape of MHC-I associated peptides presented by breast cancer tumors. Furthermore, bioinformatic analysis allowed us to identify tumor-specific and tumor associated antigens, which can be used for the development of anti-cancer vaccines or as targets for engineered T-cells.

2023-06-01 | GSE206838 | GEO

LC-MSMS of the MHC-I immunopeptidome of AML cell lines

Project description:The hypomethylating agent 5-azacytidine (AZA) is the first-line induction therapy for AML patients unsuitable for intensive chemotherapy. The anti-tumor effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, clear evidence supporting higher ERE MAPs presentation after AZA treatment in AML is lacking. Therefore, we examined the immunopeptidome of four AML cell lines treated with AZA through a proteogenomic approach to validate this hypothesis.

2024-04-17 | PXD038663 | Pride

The pancreatic islet MHC-II peptidome identifies key features of autoimmune peptides

Project description:The nature of autoantigens that trigger autoimmune diseases has been much discussed but direct biochemical identification is lacking for most. Addressing this question demands unbiased examination of the self-peptides displayed by a defined autoimmune MHC-II molecule. We have examined the immunopeptidome of the pancreatic islets of the NOD mouse that spontaneously develops autoimmune diabetes based on its MHC-II, the I-Ag7 variant. The relevant peptides that induced early CD4 T cells derived from insulin and C-peptide; these were also found in the MHC-II peptidome of the pancreatic lymph node and spleen. The insulin-derived peptides followed a trajectory from internal processing in beta cells to exocytosis, uptake, and presentation in islets and peripheral sites. Such process not only generated conventional epitopes but also resulted in presentation of post-translationally modified peptides, including deamidated and fused sequences. These analyses reveal the key features of a restricted component in the self-MHC-II peptidome causing autoreactivity.

2020-03-12 | PXD015408 | Pride

Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides

Project description:We developed a novel approach combining next generation sequencing, bioinformatics and mass spectrometry to assess the impact of non-MHC polymorphisms on the repertoire of MHC I-associated peptides (MIPs). We compared the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings and determined that MIPs mirror the genomic frequency of non-synonymous polymorphisms but they behave as recessive traits at the surface level. Moreover, we showed that 11.7% of the MIP coding exome is polymorphic at the population level. Our method provides fundamental insights into the relation between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens), which play a major role in allo-immune responses. RNA-seq of human B lymphoblasts derived from peripheral blood mononuclear cells from 2 HLA-identical female siblings.

2013-12-08 | E-GEOD-48918 | biostudies-arrayexpress

Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer

Project description:Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer

| PRJNA599422 | ENA

MHC Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T cell epitopes specific to seasonal coronaviruses and epitopes cross-reactive with SARS-CoV-2

Project description:MHC-I and MHC-II (HLA-DR and DP) immunopeptidome of hCoV-OC43 infected HEK293/CIITA/Ace2 cells

2022-10-27 | MSV000090595 | MassIVE

Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides

2013-12-08 | GSE48918 | GEO

Proteogenomics-based identification of the repertoire of human MHC class I-associated peptides

Project description:We have develop a proteogenomics-based approach for identification of human MHC class I-associated peptides, including those deriving from polymorphisms, mutations and non-canonical reading frames

2016-12-22 | GSE67174 | GEO

Multiplexed relative and absolute quantitative immunpeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition [I]

Project description:Major histocompatibility complex (MHC) class I peptides play a critical role in immune cell recognition. Cancer cells modulate surface MHC levels in response to therapy, thereby affecting antitumor immunity. However, understanding the peptide repertoire response to treatment remains challenging and is limited by quantitative mass spectrometry-based strategies lacking robust normalization controls. We describe a novel approach that leverages recombinant heavy isotope-coded peptide MHCs (hipMHCs) and multiplex isotope tagging for quantitation of peptide repertoires using low sample input. HipMHCs improve quantitative accuracy by normalizing for variation across analyses, and enable absolute quantification using internal calibrants to determine copies per cell of MHC antigens. Application of this platform to profile the immunopeptidome response to CDK4/6 inhibition and Interferon gamma, known modulators of antigen presentation, uncovered treatment-specific alterations that connect the intracellular response to extracellular immune presentation. This method quantifies repertoire changes that can inform targeted and combination immunotherapy design.

2020-04-29 | GSE144373 | GEO

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