scholarly journals Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function

2020 ◽  
Vol 21 (22) ◽  
pp. 8478
Author(s):  
Alonso Rodríguez-Caparrós ◽  
Jesús Álvarez-Santiago ◽  
María Jesús del Valle-Pastor ◽  
Carlos Suñé ◽  
Jennifer López-Ros ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Critical Role ◽  
Three Dimensional ◽  
Cell Receptor ◽  
Regulatory Elements ◽  
Thymocyte Development ◽  
Long Distance

The adaptive immune response in vertebrates depends on the expression of antigen-specific receptors in lymphocytes. T-cell receptor (TCR) gene expression is exquisitely regulated during thymocyte development to drive the generation of αβ and γδ T lymphocytes. The TCRα, TCRβ, TCRγ, and TCRδ genes exist in two different configurations, unrearranged and rearranged. A correctly rearranged configuration is required for expression of a functional TCR chain. TCRs can take the form of one of three possible heterodimers, pre-TCR, TCRαβ, or TCRγδ which drive thymocyte maturation into αβ or γδ T lymphocytes. To pass from an unrearranged to a rearranged configuration, global and local three dimensional (3D) chromatin changes must occur during thymocyte development to regulate gene segment accessibility for V(D)J recombination. During this process, enhancers play a critical role by modifying the chromatin conformation and triggering noncoding germline transcription that promotes the recruitment of the recombination machinery. The different signaling that thymocytes receive during their development controls enhancer activity. Here, we summarize the dynamics of long-distance interactions established through chromatin regulatory elements that drive transcription and V(D)J recombination and how different signaling pathways are orchestrated to regulate the activity of enhancers to precisely control TCR gene expression during T-cell maturation.

scholarly journals Identification of a Late Stage of Small Noncycling pTα−  Pre-T Cells as Immediate Precursors of T Cell Receptor α/β+  Thymocytes

1998 ◽  
Vol 188 (8) ◽  
pp. 1401-1412 ◽  
Author(s):  
César Trigueros ◽  
Almudena R. Ramiro ◽  
Yolanda R. Carrasco ◽  
Virginia G. de Yebenes ◽  
Juan P. Albar ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Developmental Model ◽  
Developmental Expression ◽  
Thymocyte Development ◽  
Cell Stage

During thymocyte development, progression from T cell receptor (TCR)β to TCRα rearrangement is mediated by a CD3-associated pre-TCR composed of the TCRβ chain paired with pre-TCRα (pTα). A major issue is how surface expression of the pre-TCR is regulated during normal thymocyte development to control transition through this checkpoint. Here, we show that developmental expression of pTα is time- and stage-specific, and is confined in vivo to a limited subset of large cycling human pre-T cells that coexpress low density CD3. This restricted expression pattern allowed the identification of a novel subset of small CD3− thymocytes lacking surface pTα, but expressing cytoplasmic TCRβ, that represent late noncycling pre-T cells in which recombination activating gene reexpression and downregulation of T early α transcription are coincident events associated with cell cycle arrest, and immediately preceding TCRα gene expression. Importantly, thymocytes at this late pre-T cell stage are shown to be functional intermediates between large pTα+ pre-T cells and TCRα/β+ thymocytes. The results support a developmental model in which pre-TCR–expressing pre-T cells are brought into cycle, rapidly downregulate surface pre-TCR, and finally become small resting pre-T cells, before the onset of TCRα gene expression.

scholarly journals Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression: Implications for HIV pathogenesis

1998 ◽  
Vol 95 (6) ◽  
pp. 3111-3116 ◽  
Author(s):  
L. Flamand ◽  
R. W. Crowley ◽  
P. Lusso ◽  
S. Colombini-Hatch ◽  
D. M. Margolis ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hiv Pathogenesis ◽  
Cd8 T Lymphocytes

scholarly journals p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement.

1996 ◽  
Vol 183 (4) ◽  
pp. 1923-1928 ◽  
Author(s):  
D Jiang ◽  
M J Lenardo ◽  
J C Zúñiga-Pflücker
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
T Cell Development ◽  
P53 Gene ◽  
Cell Receptor ◽  
Cell Development ◽  
Beta Chain ◽  
Thymocyte Development ◽  
B And T Lymphocytes

Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4-CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4-CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes.

scholarly journals A dynamical model of TCRβ gene recombination: Coupling the initiation of Dβ-Jβ rearrangement to TCRβ allelic exclusion

2017 ◽  
Author(s):  
Sébastien Jaeger ◽  
Ricardo Lima ◽  
Arnaud Meyroneinc ◽  
Marie Bonnet ◽  
Edgardo Ugalde ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Biological System ◽  
Cell Receptor ◽  
Allelic Exclusion ◽  
Dna Rearrangement ◽  
Gene Recombination

AbstractOne paradigm of random monoallelic gene expression is that of T-cell receptor (TCR)β allelic exclusion in T lymphocytes. However, the dynamics that sustain asymmetric choice in TCRβ dual allele usage and the production of TCRβ monoallelic expressing T-cells remain poorly understood. Here, we develop a computational model to explore a scheme of TCRβ allelic exclusion based on the stochastic initiation of DNA rearrangement [V(D)J recombination] at homologous alleles in T-cell progenitors, and thus account for the genotypic profiles typically associated with allelic exclusion in differentiated T-cells. Disturbances in these dynamics at the level of an individual allele have limited consequences on these pro1les, robust feature of the system that is underscored by our simulations. Our study predicts a biological system in which locus-specific, prime epigenetic allelic activation effects set the stage to both optimize the production of TCRβ allelically excluded T-cells and curtail the emergence of their allelically included counterparts.

scholarly journals Activation of cytotoxic T-cell receptor    T lymphocytes in response to specific stimulation in myelodysplastic syndromes

Haematologica ◽  
2008 ◽  
Vol 93 (3) ◽  
pp. 381-389 ◽  
Author(s):  
J.-J. Kiladjian ◽  
G. Visentin ◽  
E. Viey ◽  
S. Chevret ◽  
V. Eclache ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Myelodysplastic Syndromes ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Specific Stimulation

scholarly journals Peripheral CD25 positive T lymphocytes with biased T cell receptor V  gene usage in autoimmune endogenous posterior uveitis

1995 ◽  
Vol 48 (1) ◽  
pp. M46-M50 ◽  
Author(s):  
P J Tighe ◽  
J V Forrester ◽  
J Liversidge ◽  
H F Sewell
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Posterior Uveitis ◽  
Gene Usage ◽  
V Gene

The T Cell Receptor: Its Repertoire and Role in Thymocyte Development

1987 ◽  
pp. 1-12 ◽  
Author(s):  
Philippa Marrack ◽  
Marcia McDuffie ◽  
Willi Born ◽  
Marica Blackman ◽  
Charles Hannum ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Thymocyte Development
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