Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TCR⁺/BCR⁺ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes.

ABSTRACT: 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.

SUBMITTER: Japp AS

PROVIDER: S-EPMC8016147 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.

Project description:T and B cells are the two known lineages of adaptive immune cells. Here, we describe a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of both B and T cells. In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site. Molecular dynamics simulations revealed that this peptide has an optimal binding register for diabetogenic HLA-DQ8. In concordance, a synthetic version of the peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D patients, but not healthy controls. Moreover, mAbs bearing this clonotype are autoreactive against CD4 T cells and inhibit insulin tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute, and violators of this paradigm are likely key drivers of autoimmune diseases.

| S-EPMC7962621 | biostudies-literature

A double Philadelphia chromosome-positive chronic myeloid leukemia patient, co-expressing P210BCR-ABL1 and P195BCR-ABL1 isoforms.

Project description: Not available

| S-EPMC6278977 | biostudies-literature

Expansion of FasL-Expressing CD5+ B Cells in Type 1 Diabetes Patients.

Project description:Fas ligand drives insulitis in the non-obese diabetic mouse model of type 1 diabetes (T1D) and negatively regulates IL-10-producing (IL-10pos) CD5+ B cells in pancreata. Relevance of these phenomena to the human disease is poorly understood. Here, using splenocytes from T1D, autoantibody (Ab+), and non-diabetic (ND) human subjects, we show that a subpopulation of CD5+ B cells that is characterized by expression of FasL (FasLhiCD5+) was significantly elevated in T1D subjects, many of whom had significantly reduced frequency of IL-10posCD5+ B cells compared to Ab+ subjects. The majority of FasLhiCD5+ B cells did not produce cytokines and were more highly resistant to activation-induced cell death than their IL-10posCD5+ counterparts. These results associate expansion of FasL-expressing CD5+ B cells with T1D and lay the groundwork for future mechanistic studies to understand specific role in disease pathogenesis.

| S-EPMC5383713 | biostudies-literature

Characterization of Peripheral Blood TCR in Patients with Type 1 Diabetes Mellitus by BD RhapsodyTM VDJ CDR3 Assay.

Project description:The sequence of complementarity-determining region 3 of the T-cell receptor (TCR) varies widely due to the insertion of random bases during V-(D)-J recombination. In this study, we used single-cell VDJ sequencing using the latest technology, BD Rhapsody, to identify the TCR sequences of autoreactive T-cells characteristic of Japanese type 1 diabetes mellitus (T1DM) and to clarify the pairing of TCR of peripheral blood mononuclear cells from four patients with T1DM at the single-cell level. The expression levels of the TCR alpha variable (TRAV) 17 and TRAV21 in T1DM patients were higher than those in healthy Japanese subjects. Furthermore, the Shannon index of CD8+ T cells and FOXP3+ cells in T1DM patients was lower than that of healthy subjects. The gene expression of PRF1, GZMH, ITGB2, NKG7, CTSW, and CST7 was increased, while the expression of CD4, CD7, CD5, HLA-A, CD27, and IL-32 was decreased in the CD8+ T cells of T1DM patients. The upregulated gene expression was IL4R and TNFRSF4 in FOXP3+ cells of T1DM patients. Overall, these findings demonstrate that TCR diversity and gene expression of CD8+ and FOXP3+ cells are different in patients with T1DM and healthy subjects.

| S-EPMC9139223 | biostudies-literature

Restricted TcR β chain CDR3 clonotype is associated with resolved acute hepatitis B subjects.

Project description:BackgroundT cells play an important role in the prognosis of hepatitis B virus (HBV) infection, and are involved in the seroconversion of a patient from HBsAb negative to positive. To compare the T-cell receptor β-chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without hepatitis B surface antigen (HBsAg) convert to hepatitis B surface antibody (HBsAb), the TcRBV was determined using high throughput sequencing (HTS).MethodsThe clonotype and diversity of CDR3 in peripheral blood mononuclear cells of subjects with resolved acute hepatitis B (AHB, HBsAb+, HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq).ResultsThe overlapping rate of CDR3 clones of any two samples in AHB group was 2.00% (1.74% ~ 2.30%), CHB group was 1.77% (1.43% ~ 2.61%), and HC group was 1.82% (1.62% ~ 2.12%), and there was no significant difference among the three groups by Kruskal-Wallis H test. However, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20-1/BD1/BJ1-2) in AHB group was lower than that of HC group (P < 0.001). Moreover, exclude the 10 top clonotypes, there are 57 markedly different frequency of clones between AHB and CHB groups (18 clones up, 39 clones down), 179 (180-1) different clones between AHB and HC groups, and 134 different clones between CHB and HC groups. With regard to BV and BJ genotypes, there was no significant different frequency among the groups. Furthermore, there was no significant difference in the diversity of TcRBV CDR3 among the three groups (P > 0.05).ConclusionsThus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion of AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status.

| S-EPMC7825183 | biostudies-literature

Public TCR in EAE

Project description:Preferential use of public T cell receptors during autoimmune encephalomyelitis determined by high resolution saturating sequencing

| PRJEB13451 | ENA

Sequence and functional characterization of a public HIV-specific antibody clonotype.

Project description:Public antibody clonotypes shared among multiple individuals have been identified for several pathogens. However, little is known about the determinants of antibody "publicness". Here, we characterize the sequence and functional properties of antibodies from a public clonotype targeting the CD4 binding site on HIV-1 Env. Our results showed that HIV-1 specificity for the public antibodies studied here, comprising sequences from three individuals, was modulated by the VH, but not VL, germline gene. Non-native pairing of public heavy and light chains from different individuals suggested functional complementation of sequences within this public antibody clonotype. The strength of antigen recognition appeared to be dependent on the specific antibody light chain used, but not on other sequence features such as native-antibody or germline sequence identity. Understanding the determinants of antibody clonotype "publicness" can provide insights into the fundamental rules of host-pathogen interactions at the population level, with implications for clonotype-specific vaccine development.

| S-EPMC8692997 | biostudies-literature

GagCM9-specific CD8+ T cells expressing limited public TCR clonotypes do not suppress SIV replication in vivo.

Project description:Several lines of evidence suggest that HIV/SIV-specific CD8(+) T cells play a critical role in the control of viral replication. Recently we observed high levels of viremia in Indian rhesus macaques vaccinated with a segment of SIVmac239 Gag (Gag(45-269)) that were subsequently infected with SIVsmE660. These seven Mamu-A*01(+) animals developed CD8(+) T cell responses against an immunodominant epitope in Gag, GagCM9, yet failed to control virus replication. We carried out a series of immunological and virological assays to understand why these Gag-specific CD8(+) T cells could not control virus replication in vivo. GagCM9-specific CD8(+) T cells from all of the animals were multifunctional and were found in the colonic mucosa. Additionally, GagCM9-specific CD8(+) T cells accessed B cell follicles, the primary residence of SIV-infected cells in lymph nodes, with effector to target ratios between 20-250 GagCM9-specific CD8(+) T cells per SIV-producing cell. Interestingly, vaccinated animals had few public TCR clonotypes within the GagCM9-specific CD8(+) T cell population pre- and post-infection. The number of public TCR clonotypes expressed by GagCM9-specific CD8(+) T cells post-infection significantly inversely correlated with chronic phase viral load. It is possible that these seven animals failed to control viral replication because of the narrow TCR repertoire expressed by the GagCM9-specific CD8(+) T cell population elicited by vaccination and infection.

| S-EPMC3162554 | biostudies-literature

scRNA-seq revealed the special TCR β & α V(D)J allelic inclusion rearrangement and the high proportion dual (or more) TCR-expressing cells.

Project description:Allelic exclusion, one lymphocyte expresses one antigen receptor, is a fundamental mechanism of immunological self-tolerance and highly specific immune responses to pathogens. However, the phenomenon of V(D)J allelic inclusion (incomplete allelic exclusion or allelic escape) rearrangement and dual TCR T cells have been discovered by multiple laboratories. Despite continuous new discoveries, the proportion and underlying mechanism of dual TCR has been puzzling immunologists. In this study, we observed the presence of single T cells expressing multiple TCR chains in all samples, with the proportion of 15%, 10%, and 20% in the human thymus, human peripheral blood, and mouse lymphoid organs, respectively. The proportion of T cells possessing multiple T-cell receptors (TCR) varied significantly in different physiological states and developmental stages. By analyzing RSS category, RSS direction, and V(D)J gene position at TR locus of T cells which contain multiple TCR chains, we creatively found that one of TCR β (or TCR α) should originate from the transcription of V(D)J combination in T-cell receptor excision circle (TREC) formed after the twice successful rearrangement in the same chromosome. Moreover, human V30 (or mouse V31) gene may participate in reverse recombination and transcription to prevent allelic exclusion. In general, high proportion of T cells with multiple TCR at the transcriptome level was first made public, and we proposed a novel mechanism of secondary (or more) TCR rearrangement on a single chromosome. Our findings also indicated that the single-cell sequencing data should be classified according to the single, multiple, and abnormal TCR when analyzing the T-cell repertoire.

| S-EPMC10390570 | biostudies-literature

IMonitor: A Robust Pipeline for TCR and BCR Repertoire Analysis.

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.

| S-EPMC4596662 | biostudies-literature