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Immunopeptidome on MC38 Cell line

ABSTRACT: PTM – driven antigenicity – immunopeptidome of MC38 cell line

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Colon

SUBMITTER: Assaf Kacen

LAB HEAD: Yifat Merbl

PROVIDER: PXD017448 | Pride | 2022-10-12

REPOSITORIES: Pride

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			Action	DRS
	MC38-search.tar.gz	Other
	Seq61195_QE3.raw	Raw
	Seq61196_QE3.raw	Raw
	Seq61197_QE3.raw	Raw
	Seq61198_QE3.raw	Raw

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Publications

Post-translational modifications reshape the antigenic landscape of the MHC I immunopeptidome in tumors.

Kacen Assaf A Javitt Aaron A Kramer Matthias P MP Morgenstern David D Tsaban Tomer T Shmueli Merav D MD Teo Guo Ci GC da Veiga Leprevost Felipe F Barnea Eilon E Yu Fengchao F Admon Arie A Eisenbach Lea L Samuels Yardena Y Schueler-Furman Ora O Levin Yishai Y Nesvizhskii Alexey I AI Merbl Yifat Y

Nature biotechnology 20221006 2

Post-translational modification (PTM) of antigens provides an additional source of specificities targeted by immune responses to tumors or pathogens, but identifying antigen PTMs and assessing their role in shaping the immunopeptidome is challenging. Here we describe the Protein Modification Integrated Search Engine (PROMISE), an antigen discovery pipeline that enables the analysis of 29 different PTM combinations from multiple clinical cohorts and cell lines. We expanded the antigen landscape, ...[more]

PMID: 36203013

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Limiting the buffer function of HSP90 enhances tumor immunogenicity

Project description:MC38 cells were treated with HSP90 inhibitor and antigen repertoires were analyzed via mass spectrometry.

2019-06-26 | PXD009542 | Pride

LC-MSMS of the MHC-I immunopeptidome of murine thymic epithelial cells

Project description:Antigen presentation by cortical and medullary thymic epithelial cells (cTEC and mTEC) ensures the formation of a self-restricted and self-tolerant T cell repertoire, respectively. As such, a broad diversity of self-antigens needs to be presented by mTEC to induce T cell’s self-tolerance. Even though the expression and antigen presentation of protein coding genes in mTEC has been abundantly described, little is known of the implication of allegedly noncoding regions of the genome to tolerance induction. In this study, we focused on transposable elements (TE), which have been shown to be highly expressed by mTEC.

2024-04-17 | PXD042241 | Pride

Longitudinal expression data from CD8+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

Project description:During acute viral infections, naïve CD8+ T cells differentiate into effector CD8+ T cells and, after viral control, into memory CD8+ T cells. Memory CD8+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD8+ T cells become “exhausted” and have poor effector function, express multiple inhibitory receptors, possess low proliferative capacity, and cannot persist without antigen. To compare the development of functional memory T cells with poorly functional exhausted T cells, we generated longitudinal transcriptional profiles for each. Naive CD44Lo CD8+ T cells were isolated and sorted from uninfected C57BL/6 mice and H2-Db GP33-specific CD8+ T cells were sorted using MHC-I tetramers at d6, 8, 15, and 30 p.i. with either LCMV Arm or LCMV clone 13. RNA from these CD8+ T cells was processed, amplified, labeled, and hybridized to Affymetrix GeneChip MoGene 1.0 st microarrays

2012-11-23 | E-GEOD-41867 | biostudies-arrayexpress

CD4+ and CD8+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2012-12-19 | E-GEOD-41870 | biostudies-arrayexpress

Mapping of immunopeptidome of cancer immunotherapy with oncolytic virus and checkpoint blockade

Project description:The elucidation of therapy-induced changes to the class I major histocompatibility complex (MHC-I)-bound tumor antigens is crucial for understanding immune-mediated tumor eradication and identifying potential targets for peptide vaccines to enhance the efficacy of immunotherapies. Here, we investigated how oncolytic reovirus therapy with and without immune checkpoint blockade (ICB) alters the tumor peptide-MHC repertoire. Using mass spectrometry analysis of immunoaffinity purified MHC peptides, we first showed that changes to the MHC immunopeptidome following reovirus treatment is cancer type-dependent, where a murine fibrosarcoma model displayed quantitative and qualitative variance in differentially expressed peptides (DEPs) as compared to those identified in a murine ovarian cancer model. We then determined that the combination therapy of reovirus and ICB in the fibrosarcoma model resulted in higher numbers of DEPs relative to either monotherapy alone. Most importantly, we identified reovirus and ICB-induced MHC peptides that are biologically active in stimulating interferon-gamma response in cognate CD8+ T cells, which likely contribute to cancer immunoediting. These findings highlight the importance of therapy-induced changes to the MHC immunopeptidome in shaping the underlying anti-tumor immune responses during reovirus and ICB combination therapy.

2021-12-06 | PXD024369 | Pride

Effect of MHC II expression in pro-B cells: Pre-B cells and follicular B cells from wild-type and MHC II conditional mice

Project description:Hardy’s Fraction D bone marrow pre-B cells and splenic follicular B cells were purified by flow cytometry according to MHC II expression from wild-type and ItgaxcreH2-Ab1c MHC II conditional mice and transcriptionally profiled by RNA-seq. Duplicate or triplicate samples for each genotype and level of MHC II expression were sequenced. This is part of ongoing investigation of a possible cell-intrinsic role of MHC II B cells.

2018-08-07 | E-MTAB-6765 | biostudies-arrayexpress

MS-rescue: A Computational Pipeline to Increase the Quality and Yield of Immunopeptidomics Experiments, part 2

Project description:We propose a new pipeline for the refinement of spectrum-peptide assignment, designed specifically for MHC ligand identification. By modeling the peptidome as a collection of a limited number of specificities, corresponding to the MHC alleles of the cell line, our method achieves increased sequencing depth, while at the same time removing potential experimental outliers and contaminants.

2019-01-02 | PXD011794 | Pride

A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

Project description:Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS), but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation. To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell responses in two patients. By characterizing a large panel of NZM-specific monoclonal antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM idiotype. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supported by structural data. Interestingly, in both patients, the analysis of the CD4+ T cell response, combined with mass spectrometry-based peptidomics, revealed a single immunodominant T cell epitope spanning the FR2-CDR2 region of the NZM light chain. Moreover, a CDR2-modified version of NZM was not recognized by T cells, while retaining binding to α4 integrins. Collectively, our integrated analysis identifies the basis of T-B collaboration that leads to ADA-mediated therapeutic resistance and delineates an approach to design novel deimmunized antibodies for autoimmune disease and cancer treatment.

2019-10-10 | PXD013599 | Pride

Deciphering and predicting CD4+ T cell immunodominance of Influenza virus hemagglutinin

Project description:The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naïve and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naïve and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naïve CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naïve T cells specific for cryptic H1-HA peptides, and demonstrate that antigen processing represents a major constraint determining immunodominance.

2020-06-29 | PXD018151 | Pride

Effect of MHC II expression in pro-B cells: F6 leukaemic cell line

Project description:F6 murine leukaemic cells were transfected either with MHC II or with GFP and transcriptionally profiled by RNA-seq. Triplicate samples for each genotype were sequenced. This is part of ongoing investigation of a possible cell-intrinsic role of MHC II B cells.

2018-08-07 | E-MTAB-6763 | biostudies-arrayexpress