scholarly journals RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease

2017 ◽  
Vol 64 (4) ◽  
pp. 476-481 ◽  
Author(s):  
Jerome Bouquet ◽  
Jennifer L. Gardy ◽  
Scott Brown ◽  
Jacob Pfeil ◽  
Ruth R. Miller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Disease ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Rna Seq ◽  
Viral Pathogen ◽  
Complex Chronic Disease

Alteration of the gene expression profile of T-cell receptor αβ-modified T-cells with diffuse large B-cell lymphoma specificity

Hematology ◽  
2013 ◽  
Vol 18 (3) ◽  
pp. 138-143 ◽  
Author(s):  
Xianfeng Zha ◽  
Qingsong Yin ◽  
Huo Tan ◽  
Chunyan Wang ◽  
Shaohua Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals T-Cell Receptor Engagement Confers Resistance to Chemotherapy in T-Cell Lymphoproliferative Disorders

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2959-2959
Author(s):  
Tianjiao Wang ◽  
Avery Polk ◽  
Ye Lu ◽  
Ryan A Wilcox
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
B Cell ◽  
Signaling Pathways ◽  
T Cell Receptor ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Signaling ◽  
Antigen Receptor Signaling

Abstract Background: Chemotherapy resistance and primary refractory disease are common among patients with the more common peripheral T-cell lymphomas (TCL) treated with anthracycline-based chemotherapy. Antigen-receptor signaling activates a number of proliferation and survival pathways in normal lymphocytes. When activated in lymphomas, antigen-receptor signaling might confer resistance to chemotherapy. Until recently, the role of antigen-receptor signaling in B-cell malignancies was poorly understood. It is now appreciated that B-cell receptor (BCR) signaling is an important driver of B-cell lymphoma growth and survival, and represents an attractive therapeutic target in these lymphomas. In contrast, the potential role of T-cell receptor (TCR) signaling in T-cell lymphomagenesis is poorly understood. The observation that most (≈95%) TCLs express an intact TCR suggests that malignant T cells, like their B-cell counterparts, may benefit from antigen-receptor signaling. Methods: TCL cell lines and primary patient specimens were subjected to TCR activation by CD3/CD28 beads. Gene expression profiling was performed by Affymetrix human gene 2.1 ST array at different time points (4, 8, 24 hours) following TCR engagement. Results were further validated by immunophenotyping by flow cytometry, western blot and cytokine measurement by enzyme-linked immunosorbent assay (ELISA). The proliferation and chemoresistance of the TCL cells following TCR engagement were determined by MTT assay. Results: Microarray gene expression profiling of TCLs showed differential gene expression upon TCR engagement by CD3/CD28 beads at different time points. A total of 1274 genes were differentially expressed commonly in the patient specimens. Some of the differentially expressed genes were confirmed in independent samples by immunophenotyping (CD25, CD30, CD69, CD137, CCR4, GITR) and cytokine (IL2, IL13, IL10, IFNγ) release. Gene enrichment analysis of the common differentially expressed genes showed that pro-proliferation and pro-survival signaling pathways, including TCR (FDR: 0.05%), MAPK (FDR: 2.8%), NFκB (FDR: 0.1%) and cytokines (FDR: 0.03%) were enriched in TCR-engaged TCL cells. The activation of TCR and NFκB signaling in TCR-engaged TCLs was also confirmed by western blot and flow cytometry. More importantly, the proliferation of TCLs increased by 2-4 fold when cocultured with CD3/CD28 beads for 72 hours (p<0.01). In the presence of either vincristine or romidepsin, the viability of TCLs increased by 1.5-4 fold by CD3/CD28 bead treatment (p<0.01). TCR-dependent proliferation and chemoresistance in TCLs was significantly inhibited by agents targeting TCR and NFκB signaling pathways. Conclusions: T-cell receptor dependent signaling pathways are rational therapeutic targets in the T-cell lymphomas. Disclosures No relevant conflicts of interest to declare.

scholarly journals T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 340
Author(s):  
Ming Liang Oon ◽  
Jing Quan Lim ◽  
Bernett Lee ◽  
Sai Mun Leong ◽  
Gwyneth Shook-Ting Soon ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Copy Number ◽  
Nk Cell ◽  
Cell Receptor ◽  
T Cell Lymphomas ◽  
Number Variation ◽  
Diagnostic Applications ◽  
Cell Clonality

T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination.

scholarly journals Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways

PROTEOMICS ◽  
2009 ◽  
Vol 9 (13) ◽  
pp. 3549-3563 ◽  
Author(s):  
Masaki Matsumoto ◽  
Koji Oyamada ◽  
Hidehisa Takahashi ◽  
Takamichi Sato ◽  
Shigetsugu Hatakeyama ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Signaling Pathways ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Proteomic Analysis ◽  
Large Scale ◽  
Cell Receptor ◽  
Receptor Activation ◽  
B Cell Receptor

Ig alpha and Ig beta are functionally homologous to the signaling proteins of the T-cell receptor

1994 ◽  
Vol 14 (2) ◽  
pp. 1095-1103
Author(s):  
A L Burkhardt ◽  
T Costa ◽  
Z Misulovin ◽  
B Stealy ◽  
J B Bolen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Antigen Receptors ◽  
Cell Antigen

Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction with Src homology 2 domain-containing proteins. However, the degree of similarity between the different receptor-associated proteins varies from that of T-cell receptor (TCR) zeta and Fc receptor RIIIA gamma chains, which are homologous, to the distantly related Ig alpha and Ig beta proteins of the B-cell antigen receptor. To determine whether T- and B-cell antigen receptors are in fact functionally homologous, we have studied signal transduction by chimeric immunoglobulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that Ig alpha and Ig beta cytoplasmic domains were able to activate Ca2+ flux, interleukin-2 secretion, and phosphorylation of the same group of cellular substrates as the TCR in transfected T cells. Chimeric proteins were then used to examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP directly without involvement of TCR components. Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. We conclude that Fyn and Lck are able to recognize a clustered nonphosphorylated immune recognition receptor, but activation of these kinases is not sufficient to induce cellular responses such as Ca2+ flux and interleukin-2 secretion. In addition, the molecular structures involved in antigen receptor signaling pathways are conserved between T and B cells.

scholarly journals The ht beta gene encodes a novel CACCC box-binding protein that regulates T-cell receptor gene expression

1993 ◽  
Vol 13 (9) ◽  
pp. 5691-5701
Author(s):  
Y Wang ◽  
J A Kobori ◽  
L Hood
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Binding Protein ◽  
Cell Receptor ◽  
Regulatory Function ◽  
Human T Cell ◽  
Alpha Gene ◽  
Beta Gene

A gene encoding a novel CACCC box-binding protein that binds to the promoter region of the human T-cell receptor (TCR) V beta 8.1 gene and the mouse TCR alpha gene silencer has been cloned. This gene, termed ht beta, contains four zinc fingers of the class Cys2-X12-His2 that may be responsible for DNA binding and a highly negatively charged region that defines a putative transcriptional activation domain. Analysis of the expression of ht beta mRNA revealed similar expression levels and patterns in various cell lines. The bacterially expressed ht beta protein can bind to the CACCC box in both the human TCR V beta 8.1 gene promoter and the mouse TCR alpha gene silencer. The CACCC box is essential for efficient transcription of the V beta 8.1 promoter. Cotransfection with an ht beta expression plasmid and a reporter vector indicated that ht beta can activate human TCR V beta 8.1 gene transcription. ht beta also is able to counteract the silencing effect of the mouse TCR alpha gene silencer. The CACCC box has been found in almost all V beta 8.1 gene subfamily members and in both TCR alpha and beta gene enhancers in humans and mice. These results suggest that the CACCC box-binding protein may have an important regulatory function for TCR gene expression in alpha beta T cells versus gamma delta T cells.

Analysis of immunoglobulin and T-cell receptor gene deficiency in graft rejection by gene expression profiles1

2004 ◽  
Vol 77 (4) ◽  
pp. 580-586 ◽  
Author(s):  
Rachel A. DeFina ◽  
Yurong Liang ◽  
Hongzhen He ◽  
Kathleen J. Haley ◽  
Kenneth Christopher ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Rejection ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Gene Deficiency ◽  
T Cell Receptor Gene ◽  
Cell Receptor Gene

scholarly journals Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL

2018 ◽  
Vol 7 (6) ◽  
pp. e1432328 ◽  
Author(s):  
Gonzalo Blanco ◽  
Anna Vardi ◽  
Anna Puiggros ◽  
Andrea Gómez-Llonín ◽  
Manuel Muro ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Early Stage ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes

1990 ◽  
Vol 10 (10) ◽  
pp. 5486-5495
Author(s):  
L R Gottschalk ◽  
J M Leiden
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Receptor ◽  
Binding Sites ◽  
Cell Receptor ◽  
Nuclear Proteins ◽  
Transcriptional Enhancer ◽  
Enhancer Element ◽  
Beta 2 ◽  
Beta Gene

A transcriptional enhancer has been mapped to a region 5.5 kilobases 3' of the C beta 2 gene in the human T-cell receptor (TCR) beta-chain locus. Transient transfections allowed localization of enhancer activity to a 480-base-pair HincII-XbaI restriction enzyme fragment. The TCR beta enhancer was active on both the minimal simian virus 40 promoter and a TCR beta variable gene promoter in both TCR alpha/beta + and TCR gamma/delta + T cells. It displayed significantly less activity in Epstein-Barr virus-transformed B cells and K562 chronic myelogenous leukemia cells and no activity in HeLa fibroblasts. DNA sequence analysis revealed that the enhancer contains a consensus immunoglobulin kappa E2 motif, as well as an AP-1-binding site and a cyclic AMP response element. DNase I footprint analyses using Jurkat T-cell nuclear extracts allowed the identification of five nuclear protein-binding sites, T beta 1 to T beta 5, within the enhancer element. Deletion and in vitro mutagenesis studies demonstrated that the T beta 2- and T beta 3- and T beta 4-binding sites are each required for full transcriptional enhancer activity. In contrast, deletion of the T beta 1- and T beta 5-binding sites had essentially no effect on enhancer function. Electrophoretic mobility shift assays demonstrated that TCR alpha/beta + and TCR gamma/delta + T cells expressed T beta 2-, T beta 3-, and T beta 4-binding activities. In contrast, non-T-cell lines, in which the enhancer was inactive, each lacked expression of at least one of these binding activities. TCR alpha and beta gene expression may be regulated by a common set of T-cell nuclear proteins in that the T beta 2 element binding a set of cyclic AMP response element-binding proteins that are also bound by the T alpha 1 element of the human TCR alpha enhancer and the decamer element present in a large number of human and murine TCR beta promoters. Similarly, the T beta 5 TCR beta-enhancer element and the T alpha 2 TCR alpha-enhancer element bind at least one common T-cell nuclear protein. Taken together, these results suggest that TCR beta gene expression is regulated by the interaction of multiple T cell nuclear proteins with a transcriptional enhancer element located 3' of the C beta 2 gene and that some of these proteins may be involved in the coordinate regulation of TCR alpha and beta gene expression.

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