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
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Human Coronavirus Oc43 (ncbitaxon:31631)
SUBMITTER: 
Lawrence J. Stern
PROVIDER: MSV000090595 | MassIVE | Thu Oct 27 07:07:00 BST 2022
SECONDARY ACCESSION(S): PXD037779
REPOSITORIES: MassIVE
Similar Datasets
Project description:APCs (A20/ DCs) were stimulated by adjuvants, CpG, MDP and MPLA respectively for 12h. Then MHC-II Immunopeptidome and proteome were perforemd
2024-10-30 | PXD052277 |
Project description:Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer
| PRJNA599422 | ENA
Project description:Tumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of the genome. Motivated by the recent discovery of translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized that cancer-associated processes could generate nuORFs that can serve as a new source of tumor antigens that harbor somatic mutations or show tumor-specific expression. To identify cancer-specific nuORFs, we generated Ribo-seq profiles for 29 malignant and healthy samples. These included primary normal and chronic lymphocytic leukemia (CLL) B cells, patient-derived primary glioblastoma (GBM) and melanoma cell cultures, primary healthy melanocytes, as well as established colon carcinoma and melanoma cell lines. These also included B721.221 cells, the parental cell line previously used to generate 92 single HLA allele-expressing lines from which we collected mono-allelic MHC I immunopeptidome data. We developed a hierarchical approach to identify translated novel unannotated open reading frames that leverages the large amount of Ribo-seq data we have generated in order to uncover lowly expressed nuORFs, while also preserving tissue specificity. We constructed a database of novel unannotated ORFs (nuORFdb) and used it to analyze mass spectrometry datasets of MHC I-bound peptides, where we detected peptides from 3,555 nuORFs. Additionally, we used nuORFdb to identify cancer-specific nuORFs, as well as nuORFs harboring cancer-specific somatic variants as potential sources of neoantigens in cancer. *This repository contains data from the publicly available cell lines used in this study, including B721.221 cells, A375 cells, HCT116 cells and primary healthy melanocytes (Thermo C0025C). The data pertaining to primary patient samples that are part of this study is deposited in dbGaP.
2020-08-01 | GSE143263 | GEO
Project description:The major histocompatibility complex class I (MHC-I) antigen presentation pathways play pivotal roles in orchestrating immune responses. Recent studies have begun to utilize cysteines within the immunopeptidome for therapeutic applications, such as using covalent ligands to create haptenated neoantigens for inducing an immune response. In this study, we report a platform for mapping reactive cysteines present on MHC-I-bound peptide antigens. We have developed cell-impermeable sulfonated maleimide probes capable of effectively capturing reactive cysteines on antigens. Utilizing these probes in chemoproteomic experiments, we discovered that cysteines on MHC-I-bound antigens exhibit various degrees of reactivity. Furthermore, interferon-gamma stimulation produces increased reactivity of cysteines at position 8 of 9-mer MHC-I-bound antigens. Our findings may open up new avenues for understanding the distinctive roles of cysteine within the MHC-I immunopeptidome and leveraging the differentially reactive cysteines for therapeutic intervention.
2024-10-17 | PXD054678 | Pride
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
Project description:The array of peptides presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC class I immunopeptidome. Although the MHC class I immunopeptidome is ubiquitous in mammals and represents a critical component of the adaptive immune system, very little is known about its baseline composition across all tissues and organs in vivo. In this study, we applied mass spectrometry (MS) technologies to draft a tissue-based atlas of the MHC class I immunopeptidome in the C56BL/6 mouse model. Overall, 19 normal mouse tissues were extracted and a total number of ~30,000 high-confidence H2Db/Kb-associated peptides were identified and annotated in the atlas. The raw MS output files, the catalogue of H2Db/Kb-associated peptides, the tissue origin(s) of individual peptides and the H2Db/Kb-specific peptide spectral libraries, which consist of consensus spectra calculated from repeat measurements of the same peptide sequence, were shared via the SysteMHC Atlas project (dataset identifier SYSMHC00018). We expect that this unique dataset will be further expended in the future and will be re-used by the community to 1) investigate the tissue-specificity of the immunopeptidome, 2) perform highly reproducible spectral library-based analysis of immunopeptidomes from mice cohorts, and 3) rapidly identify disease-specific H2Db/Kb peptide antigens from various mouse models of autoimmune diseases and cancers.
2018-06-19 | PXD008733 | Pride
Project description:The array of peptides presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC class I immunopeptidome. Although the MHC class I immunopeptidome is ubiquitous in mammals and represents a critical component of the adaptive immune system, very little is known about its baseline composition across all tissues and organs in vivo. In this study, we applied mass spectrometry (MS) technologies to draft a tissue-based atlas of the MHC class I immunopeptidome in the C56BL/6 mouse model. Overall, 19 normal mouse tissues were extracted and a total number of ~30,000 high-confidence H2Db/Kb-associated peptides were identified and annotated in the atlas. The raw MS output files, the catalogue of H2Db/Kb-associated peptides, the tissue origin(s) of individual peptides and the H2Db/Kb-specific peptide spectral libraries, which consist of consensus spectra calculated from repeat measurements of the same peptide sequence, were shared via the SysteMHC Atlas project (dataset identifier SYSMHC00018). We expect that this unique dataset will be further expended in the future and will be re-used by the community to 1) investigate the tissue-specificity of the immunopeptidome, 2) perform highly reproducible spectral library-based analysis of immunopeptidomes from mice cohorts, and 3) rapidly identify disease-specific H2Db/Kb peptide antigens from various mouse models of autoimmune diseases and cancers.
2020-02-19 | MSV000084980 | MassIVE
Project description:By using >36,000 immunogenicity assay results, we developed a method to identify peptide-MHC complexes whose structural alignment facilitates T cell reaction. Our method accurately predicted neoepitopes for MHC II as well as MHC I that were responsive to checkpoint blockade when applied to >1,200 samples of various tumor types and on-therapy melanoma samples. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of >25 million mutations in >9,000 treatment-naïve tumors in association with >100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure particularly with high TCR clonality and MHC II expression.
| EGAS00001006445 | EGA
Project description:Characterisation of peptide ligands of Major histocompatibility class (MHC) I isolated by immunoaffinity purification from the C1R (Class I reduced) B-lymphoblastoid cell line, transfected with the MHC class I allele HLA-A*01:01, or HLA-A*02:01, HLA-A*24:02. In addition, public mass spectrometry (MS) datasets of HLA-I and HLA-II immunopeptidome derived from patients’ samples, PBMC or cell lines, and shotgun proteomics from trypsin/elastase digestion were analysed.
2020-07-27 | PXD014754 | Pride
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