Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883398 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Antigen-specific T-cell receptor signatures of cytomegalovirus infection
| PRJNA473147 | ENA
Project description:Accurately assigning antigen specificity to T cell receptor (TCR) sequences is challenging due to the complexity of the TCR-antigen recognition process in humans. We developed the Peptide-Driven Identification of TCRs (PDI-TCR) assay, a novel method combining in vitro expansion with peptide pools, bulk TCR sequencing, and statistical analysis to identify antigen-specific TCRs from human blood. A key feature of PDI-TCR is its ability to account for bystander T cell expansion using both antigen-specific and non-specific peptide pools, distinguishing true antigen-specific TCRs from the unspecific ones. We applied PDI-TCR to Tuberculosis (TB) patients, sampling blood at diagnosis and throughout therapy, and Mycobacterium tuberculosis (Mtb)-sensitized healthy individuals (IGRA+). We identified hundreds of Mtb-specific and unspecific TCRs, and in combination with single-cell mRNA and TCR sequencing of CD4 T cells, we characterized the transcriptome of Mtb-specific and unspecific T cells in each cohort. Mtb-specific T cells were highly diverse, with the presence of short-lived effector phenotypes only in TB at diagnosis and memory phenotypes maintained through treatment. In contrast, unspecific T cells were more clonally restricted and expanded, cytotoxic, and maintained through treatment. Thus, PDI-TCR is a powerful tool for identifying antigen-specific TCRs. Combined with single-cell sequencing of T cell populations, it enables direct ex vivo monitoring of antigen-specific T cells.
2025-04-30 | GSE293807 | GEO
Project description:T-cell receptor beta CDR3 sequencing of tumor-associated antigen and minor histocompatibility antigen specific T cells
| PRJEB38225 | ENA
Project description:Cells communicate with each other via receptor-ligand interactions. Here we describe lentiviral-mediated cell e¬ntry by engineered receptor-ligand interaction (ENTER) to display ligand proteins, deliver payloads, and record receptor specificity. We optimize ENTER to decode interactions between T cell receptor (TCR)-MHC peptides, antibody-antigen, and other receptor-ligand pairs. A viral presentation strategy allows ENTER to capture interactions between B cell receptor and any antigen. We engineer ENTER to deliver genetic payloads to antigen-specific T or B cells to selectively modulate cellular behavior in mixed populations. Single-cell readout of ENTER by RNA-sequencing (ENTER-seq) enables multiplexed enumeration of antigen specificities, TCR clonality, cell-type and states of individual T cells. ENTER-seq of CMV-seropositive patient blood samples reveals the viral epitopes that drive effector memory T cell differentiation and inter- vs intra-clonal phenotypic diversity targeting the same epitope. ENTER technology enables systematic discovery of receptor specificity, linkage to cell fates, and antigen-specific cargo delivery.
2022-12-12 | GSE212996 | GEO
Project description:Cells communicate with each other via receptor-ligand interactions. Here we describe lentiviral-mediated cell e¬ntry by engineered receptor-ligand interaction (ENTER) to display ligand proteins, deliver payloads, and record receptor specificity. We optimize ENTER to decode interactions between T cell receptor (TCR)-MHC peptides, antibody-antigen, and other receptor-ligand pairs. A viral presentation strategy allows ENTER to capture interactions between B cell receptor and any antigen. We engineer ENTER to deliver genetic payloads to antigen-specific T or B cells to selectively modulate cellular behavior in mixed populations. Single-cell readout of ENTER by RNA-sequencing (ENTER-seq) enables multiplexed enumeration of antigen specificities, TCR clonality, cell-type and states of individual T cells. ENTER-seq of CMV-seropositive patient blood samples reveals the viral epitopes that drive effector memory T cell differentiation and inter- vs intra-clonal phenotypic diversity targeting the same epitope. ENTER technology enables systematic discovery of receptor specificity, linkage to cell fates, and antigen-specific cargo delivery.
2022-12-12 | GSE212984 | GEO
Project description:Single-cell RNA sequencing can to resolve transcriptional features from large numbers of individual immune cells, but techniques capable of resolving the variable regions of B cell receptors (BCR) – defining features that confer antigen specificity to B cells – remain limited, especially from widely-used 3`-barcoded libraries. Here, we report a method that for recovering paired, full-length variable region sequences of the BCRs from 3`-barcoded single-cell whole transcriptome libraries. We first verified this method could produce accurate, full-length BCR sequences. We then applied this method to profile antigen-specific B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in infant rhesus macaques. Using our method, we defined features of the BCR associated with specificity for the ST3 antigen and showed that these sequence characteristics are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and for profiling antigen-specific responses elicited by vaccination.
2023-05-19 | GSE232873 | GEO
Project description:Transcriptional responses of T cells activated via CD22-specific T cell receptor compared to CD22-specific chimeric antigen receptor
| PRJNA1074674 | ENA
Project description:B and T cells can recognise and respond to a vast array of foreign pathogens by virtue of the diverse antigen-receptor repertoire generated by gene rearrangement during development. Here, we show that deficiency in Ki67, a nuclear protein ubiquitously expressed throughout the cell cycle, impairs B-cell development at specific, early stages. We identified that Ki67 maintains global chromatin accessibility in lymphocyte progenitors at stages where antigen-receptor gene rearrangements occur and that gene rearrangement is less efficient in the absence of Ki67. That the defects in B cell development are caused by disrupted antigen-receptor gene rearrangement is shown by pre-rearranged antigen-receptor genes fully compensating for loss of Ki67. Collectively, these results identify a unique contribution from Ki67 to somatic antigen-receptor gene rearrangement.
2024-05-31 | GSE246986 | GEO
Project description:Adoptive cell therapy of donor-derived, antigen-specific T cells expressing native T cell receptors (TCRs) is a powerful strategy to fight viral infections in immunocompromised patients. Determining the fate of T cells following patient infusion hinges on the ability to track them in vivo. While this is possible by genetic labeling of parent cells, the applicability of this approach has been limited by the non-specificity of the edited T cells. Here, we devised a method for CRISPR-targeted genome integration of a barcoded gene into Epstein-Barr virus-antigen-stimulated T cells and demonstrated its use for exclusively identifying expanded virus-specific cell lineages. Our method facilitated the enrichment of antigen-specific T cells, which then mediated improved cytotoxicity against EBV-transformed target cells. Single-cell and deep sequencing for lineage tracing revealed the expansion profile of specific T cell clones and their corresponding gene expression signature. This approach has the potential to enhance the traceability and the monitoring capabilities during immunotherapeutic T cell regimens.
2023-06-17 | GSE234778 | GEO