Single cell sequencing of murine ApoB-reactive CD4+ T cells
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ABSTRACT:
PROVIDER: PRJNA627230 | ENA |
REPOSITORIES: ENA
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Project description:We report the single cell transcriptome of atherosclerosis-specific murine CD4+ T cells that recognize a peptide from ApoB-100, the core protein of low-density lipoprotein (LDL). Our data reveal a unique single cell transcriptome of ApoB-specific T cells that is similar to T-regulatory T but shows an overlap with the transcriptome of pathogenic T-helper type -1 and -17 cells on a single cell level.
2020-05-21 | GSE149068 | GEO
Project description:We report the transcriptome of atherosclerosis-specific murine CD4+ T cells in atherosclerosis that recognize a peptide from ApoB-100, the core protein of low-density lipoprotein (LDL). Our data reveal a unique transcriptome of ApoB-specific T cells that is similar to T-regulatory T cells and changes during disease progression in a pathogenic T-helper type -1 and -17 like transcriptome.
2020-05-21 | GSE149067 | GEO
Project description:RNA-sequencing of ApoB-reactive CD4+ T cells in mice
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Project description:Atherosclerosis is a major pathological condition that underlies many cardiovascular diseases (CVDs). Its etiology involves breach of tolerance to self, leading to clonal expansion of autoreactive apolipoprotein B (APOB)–reactive CD4+T cells that correlates with clinical CVD. The T-cell receptor (TCR) sequences that mediate activation of APOB-specific CD4+T cells are unknown. Methods: In a previous study, we had profiled the hypervariable complementarity determining region 3 (CDR3) of CD4+T cells that respond to six immunodominant APOB epitopes in most donors. Here, we comprehensively analyze this dataset of 149,065 APOB-reactive and 199,211 non-reactive control CDR3s from six human leukocyte antigen–typed donors. Results: We identified 672 highly expanded (frequency threshold > 1.39E-03) clones that were significantly enriched in the APOB-reactive group as compared to the controls (log10 odds ratio ≥1, Fisher’s test p < 0.01). Analysis of 114,755 naïve, 91,001 central memory (TCM) and 29,839 effector memory (TEM) CDR3 sequences from the same donors revealed that APOB+ clones can be traced to the complex repertoire of unenriched blood T cells. The fraction of APOB+ clones that overlapped with memory CDR3s ranged from 2.2% to 46% (average 16.4%). This was significantly higher than their overlap with the naïve pool, which ranged from 0.7% to 2% (average 1.36%). CDR3 motif analysis with the machine learning–based in-silico tool, GLIPHs (grouping of lymphocyte interactions by paratope hotspots), identified 532 APOB+ motifs. Analysis of naïve and memory CDR3 sequences with GLIPH revealed that ~40% (209 of 532) of these APOB+motifs were enriched in the memory pool. Network analysis with Cytoscape revealed extensive sharing of the memory-affiliated APOB+ motifs across multiple donors. We identified six motifs that were present in TCM and TEM CDR3 sequences from >80% of the donors and were highly enriched in the APOB-reactive TCR repertoire. Discussion: The identified APOB-reactive expanded CD4+T cell clones and conserved motifs can be used to annotate and track human atherosclerosis-related autoreactive CD4+T cells and measure their clonal expansion.
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Project description:Pathogenic autoimmunity in atherosclerosis evolves from initially protective ApoB-reactive CD4+ T-regulatory cells
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Project description:We sorted T-helper-1 (Th1), memory (Tmem), Treg and APOB-specific CD4 T cells, detected and sorted by a validated MHC-II tetramer DRB1*07:01 APOB-p18 (Tet+ cells) from peripheral blood mononuclear cell samples from 8 DRB1*07:01+ women with and without subclinical cardiovascular disease (sCVD) as documented by carotid artery ultrasound. We subjected them to 10x Genomics 5’ single cell RNA-sequencing with T cell receptor (TCR) sequencing.
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Project description:Acute graft versus host disease is a serious condition caused by allo-reactive donor CD4+ T cells from allogenic hematopoietic stem cell transplantation. To understand the developmental relationships between T-helper states in mesenteric lymph nodes (mLN), TCR transgenic CD4+ T cells specific for a single allo-peptide (TEa cells) from mice were recovered at Days 0, 1, 2, 3, and 4 from mLN, and Day 5 from the gut and underwent processing to generate scRNA-seq dataset. TEa cells were also recovered at Day 5 from mLN and were either treated with and without IEL-isolation pre-digestion buffer as controls.
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Project description:Single cell ATAC sequencing of SIINFEKL-reactive immune cell from intracranial murine GL261-SIINFEKL tumors 20 days after inoculation. SIINFEKL-reactive T cells were sorted based on dextramer staining. We show that loss of major histocompatibility complex (MHC) class II (MHCII)-restricted antigen presentation on bbm drives dysfunctional intratumoral tumor-reactive CD8+ T cell states through increased chromatin accessibility and expression of Tox, a critical regulator of T cell exhaustion.
2023-01-11 | E-MTAB-12512 | biostudies-arrayexpress
Project description:Islet-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects are thought to be involved in disease pathogenesis, but full understanding of their role is complicated by their presence also in blood of in healthy subjects. To elucidate their role in T1D, we have combined flow cytometry and single cell RNA sequencing (RNA-seq) techniques to link prior antigen exposure, inferred from expanded TCR clonotypes, and functional capacities of islet antigen-reactive CD4+ memory T cells. We find that cells activated by pooled peptides from immunodominant islet antigens showed significantly higher clonotype sharing within recent onset T1D subjects than in healthy individuals, consistent with in vivo T cell expansion during disease progression. There was no clonotype sharing between donors, indicating a predominance of TCRs with distinct or “private” specificities. Expanded clonotypes could be stable, as one was detected at repeat visits by spanning more than a year by one subject. We identified distinct IGRP peptides as the targets of expanded TCR clonotypes from two T1D subjects, thereby implicating this molecule as a trigger for CD4+ T cell expansion during T1D. Transcriptome profiles of cells from T1D and healthy subjects differed, particularly in cells having the most highly expanded TCR clonotypes. As a group, cells with the most highly expanded TCR clonotypes showed Th2-like phenotypes, but at the single cell level there was phenotypic heterogeneity within and between donors. Our findings demonstrate unique specificities and phenotypes of individual islet-reactive CD4+ memory T cells that have expanded during disease progression.
2017-06-08 | GSE96568 | GEO