Mice TCR/BCR in NUDCD3 mutants
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB55545 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR10114825_1.fastq.gz | Fastqsanger.gz | |||
| ERR10114825_2.fastq.gz | Fastqsanger.gz | |||
| ERR10114827_1.fastq.gz | Fastqsanger.gz | |||
| ERR10114827_2.fastq.gz | Fastqsanger.gz | |||
| ERR10114429_1.fastq.gz | Fastqsanger.gz |
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Project description:The advance of next generation sequencing (NGS) techniques provides an unprecedented opportunity to probe the enormous diversity of the immune repertoire by deep sequencing T-cell receptors (TCRs) and B-cell receptors (BCRs). However, an efficient and accurate analytical tool is still on demand to process the huge amount of data. We have developed a high-resolution analytical pipeline, Immune Monitor ("IMonitor") to tackle this task. This method utilizes realignment to identify V(D)J genes and alleles after common local alignment. We compare IMonitor with other published tools by simulated and public rearranged sequences, and it demonstrates its superior performance in most aspects. Together with this, a methodology is developed to correct the PCR and sequencing errors and to minimize the PCR bias among various rearranged sequences with different V and J gene families. IMonitor provides general adaptation for sequences from all receptor chains of different species and outputs useful statistics and visualizations. In the final part of this article, we demonstrate its application on minimal residual disease detection in patients with B-cell acute lymphoblastic leukemia. In summary, this package would be of widespread usage for immune repertoire analysis.
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Project description:In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. In comparison to controls, we show that RA patients have multiple and strong differences in the BCR repertoire including reduced diversity as well as altered isotype, chain and segment frequencies. We demonstrate that therapeutic TNF inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific TCR repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.
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Project description:Intestinal epithelial cells (IEC) express large amounts of major histocompatibility complex II (MHCII) molecules. Despite this long-appreciated observation, the function of epithelial MHCII-mediated signaling on gut homeostasis remains enigmatic. As IECs serve as the primary cellular barrier between intestinal microbes and underlying host immune cells, we reasoned that IEC-intrinsic antigen presentation may play a role in tolerogenic responses towards the microbiota. Mice with an IEC-intrinsic defect in MHCII expression (IECΔMHCII) develop elevated T cell-dependent IgA responses, but a reduction in microbiota responsive regulatory T cells (Tregs). Despite elevated IgA levels in IECΔMHCII mice, immunoglobulin repertoires exhibit less selection and IgA has reduced reactivity to the microbiota, which is associated with increased inter-individual variability in microbiota composition. Consistent with reductions in microbiota-responsive Tregs, IECΔMHCII mice develop worsened colitis. A striking difference observed in the absence of IEC-MHCII is that while transcription of MHCII is similar, underlying mononuclear phagocytes had reduced surface MHCII. Macrophages were found to be capable of acquiring MHCII molecules from IECs, and macrophages isolated from IECΔMHCII mice had decreased capacity to stimulate Treg development. Thus, epithelial-myeloid interactions govern development of adaptive responses to microbial antigens within the gastrointestinal tract.
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Project description:RNAseq on Dengue specific mice immunoglobulin repertoires
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Project description:IntroductionThe SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients.Materials and methodsIn this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages.ResultsExpanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased.ConclusionThis study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19.
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Project description:Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and T cell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings. While we could identify DE cells by flow cytometry, we found no association between DE cell frequency and T1D status. We were unable to identify the reported public B cell clone, or any similar clone, in bulk B cells or sorted DE cells from T1D subjects or controls. We also did not observe increased usage of the public clone VH or DH genes in B cells or in sorted DE cells. Taken together, our findings suggest that DE cells and their alleged public clonotype are not enriched in T1D. This Matters Arising paper is in response to Ahmed et al. (2019), published in Cell. See also the response by Ahmed et al. (2021), published in this issue.
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Project description:We have reported that intra-tumoral treatment with 1V270, a phospholipid-conjugated TLR7 agonist,induces local expansion an systemic dispersion of oligoclonal tumor-specific T cells by TCR repertoire analysis using next generation RNAseq methodology. Here, we examined whether systemic 1V270 therapy also induced oligoclonal expansion of tumor-specific T cells. Two groups of BALB/c mice (n=4/group) were i.p. treated with 1V270,a phospholipid-conjugated TLR7 agonist. One cohort of mice was i.v. injected with 4T1-GLF cells (2×104) on day 0. Another cohort did not receive i.v. tumor injection (no tumor-exposed mice). 4T1 cells were orthotopically inoculated on day 21. To examine clonal specificity of tumor-specific T cells, CD8+ cells were isolated from the spleens and the tumor infiltrating lymphocytes of secondarily challenged tumors after initial 1V270 therapy. The TCR repertoires were assessed by next generation RNA sequencing of both TCRαand TCR β genes.
2018-07-31 | E-MTAB-6566 | biostudies-arrayexpress