Regulation of T cell receptor (TCR)-β locus allelic exclusion and initiation of TCR-α locus rearrangement in immature thymocytes by signaling through the CD3 complex

1995 ◽  
Vol 25 (5) ◽  
pp. 1257-1261 ◽  
Author(s):  
Christiann N. Levelt ◽  
Baoping Wang ◽  
Angelika Ehrfeld ◽  
Cox Terhorst ◽  
Klaus Eichmann
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Allelic Exclusion ◽  
Immature Thymocytes

Crucial function of the pre-T-cell receptor (TCR) in TCRP selection, TCRbeta allelic exclusion and alphabeta versus gammadelta lineage commitment

1998 ◽  
Vol 165 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Harald Boehmer ◽  
Iannis Aifantis ◽  
Orly Azogui ◽  
Jacqueline Feinberg ◽  
Claude Saint-Ruf ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Lineage Commitment ◽  
Allelic Exclusion

scholarly journals The CD3-γδε and CD3-ζ/η Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor β Locus but Are Both Dispensable for the Initiation of  V to (D)J Recombination at the T Cell Receptor–β, –γ, and –δ Loci

1998 ◽  
Vol 187 (1) ◽  
pp. 105-116 ◽  
Author(s):  
Laurence Ardouin ◽  
Jamila Ismaili ◽  
Bernard Malissen ◽  
Marie Malissen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Mutant Mice ◽  
Allelic Exclusion ◽  
Gene Products ◽  
Β Chain ◽  
Deficient Mice

The pre–T cell receptor (TCR) associates with CD3-transducing subunits and triggers the selective expansion and maturation of T cell precursors expressing a TCR-β chain. Recent experiments in pre-Tα chain-deficient mice have suggested that the pre-TCR may not be required for signaling allelic exclusion at the TCR-β locus. Using CD3-ε– and CD3-ζ/η–deficient mice harboring a productively rearranged TCR-β transgene, we showed that the CD3-γδε and CD3-ζ/η modules, and by inference the pre-TCR/CD3 complex, are each essential for the establishment of allelic exclusion at the endogenous TCR-β locus. Furthermore, using mutant mice lacking both the CD3-ε and CD3-ζ/η genes, we established that the CD3 gene products are dispensable for the onset of V to (D)J recombination (V, variable; D, diversity; J, joining) at the TCR-β, TCR-γ, and TCR-δ loci. Thus, the CD3 components are differentially involved in the sequential events that make the TCR-β locus first accessible to, and later insulated from, the action of the V(D)J recombinase.

scholarly journals HES1 opposes a PTEN-dependent check on survival, differentiation, and proliferation of TCRβ-selected mouse thymocytes

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1439-1448 ◽  
Author(s):  
Gladys W. Wong ◽  
Gisele C. Knowles ◽  
Tak W. Mak ◽  
Adolfo A. Ferrando ◽  
Juan Carlos Zúñiga-Pflücker
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Akt Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Developmental Progression ◽  
Differentiation And Proliferation ◽  
Immature Thymocytes

Abstract The developmental progression of immature thymocytes requires cooperative input from several pathways, with Notch signals playing an indispensable role at the T-cell receptor (TCR)–β selection checkpoint. Notch signals affect the activation of the PI3K/Akt pathway, which is required for pTα/TCRβ (pre-TCR)–induced survival, differentiation, and proliferation of developing αβ-lineage thymocytes. However, the molecular players responsible for the interaction between the Notch and PI3K pathways at this critical developmental stage are unknown. Here, we show that Notch induction of Hes1 is necessary to repress the PI3K/Akt pathway inhibitor, PTEN (phosphatase and tensin homolog), which in turn facilitates pre-TCR–induced differentiation. In support of this mechanism, deletion or down-regulation of Pten overcomes the Notch signaling requirement for survival and differentiation during β-selection. In addition, c-Myc is a critical target of Notch at this stage, as c-Myc expression overcomes the Notch signaling requirement for proliferation during β-selection. Collectively, our results point to HES1, via repression of PTEN, and c-Myc as critical mediators of Notch function at the β-selection checkpoint.

scholarly journals Stringent V beta requirement for the development of NK1.1+ T cell receptor-alpha/beta+ cells in mouse liver.

1996 ◽  
Vol 183 (3) ◽  
pp. 1277-1282 ◽  
Author(s):  
T Ohteki ◽  
H R MacDonald
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Beta Cells ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Allelic Exclusion ◽  
Stringent Requirement ◽  
Major Subset ◽  
Alpha Beta

The liver of C57BL/6 mice contains a major subset of CD4+8- and CD4-8- T cell receptor (TCR)-alpha/beta+ cells expressing the polymorphic natural killer NK1.1 surface marker. Liver NK1.1+TCR-alpha/beta+ (NK1+ T) cells require interaction with beta2-microglobulin-associated, major histocompatibility complex I-like molecules on hematopoietic cells for their development and have a TCR repertoire that is highly skewed to Vbeta8.2, Vbeta7, and Vbeta2. We show here that congenic C57BL/6.Vbeta(a) mice, which lack Vbeta8- expressing T cells owing to a genomic deletion at the Vbeta locus, maintain normal levels of liver NK1+ T cells owing to a dramatic increase in the proportion of cells expressing Vbeta7 and Vbeta2 (but not other Vbetas). Moreover, in C57BL/6 congenic TCR-V Vbeta3 and -Vbeta8.1 transgenic mice (which in theory should not express other Vbeta, owing to allelic exclusion at the TCR-beta locus), endogenous TCR-Vbeta8.2, Vbeta7, and Vbeta2 (but not other Vbetas) are frequently expressed on liver NK1+T cells but absent on lymph node T cells. Finally, when endogenous V beta expression is prevented in TCR-Vbeta3 and Vbeta8.1 transgenic mice (by introduction of a null allele at the C beta locus), the development of liver NK1+T cells is totally abrogated. Collectively, our data indicate that liver NK1+T cells have a stringent requirement for expression of TCR-Vbeta8.2, Vbeta7, or Vbeta2 for their development.

Abrogation of the Allelic Exclusion in a T Cell Receptor β Chain Gene Transgenic Mouse Strain

1995 ◽  
Vol 24 (6) ◽  
pp. 927-946 ◽  
Author(s):  
O. Mazda ◽  
Y. Aiba ◽  
N. Hattori ◽  
M. Li ◽  
S. Fujimoto ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mouse ◽  
T Cell Receptor ◽  
Mouse Strain ◽  
Cell Receptor ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
Transgenic Mouse Strain ◽  
Β Chain

scholarly journals GATA3 Abundance Is a Critical Determinant of T Cell Receptor β Allelic Exclusion

2017 ◽  
Vol 37 (12) ◽  
Author(s):  
Chia-Jui Ku ◽  
JoAnn M. Sekiguchi ◽  
Bharat Panwar ◽  
Yuanfang Guan ◽  
Satoru Takahashi ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
The Other ◽  
Allelic Exclusion ◽  
Wild Type ◽  
Critical Determinant ◽  
Gata3 Expression ◽  
Immunological Process ◽  
Functional Receptor

ABSTRACT Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild-type mammals, approximately 60% of cells have recombined the DNA of one T cell receptor β (TCRβ) V-to-DJ-joined allele in a functional configuration, while the second allele has recombined only the DJ sequences; the other 40% of cells have recombined the V to the DJ segments on both alleles, with only one of the two alleles predicting a functional TCRβ protein. Here we report that the transgenic overexpression of GATA3 leads predominantly to biallelic TCRβ gene (Tcrb) recombination. We also found that wild-type immature thymocytes can be separated into distinct populations based on intracellular GATA3 expression and that GATA3LO cells had almost exclusively recombined only one Tcrb locus (that predicted a functional receptor sequence), while GATA3HI cells had uniformly recombined both Tcrb alleles (one predicting a functional and the other predicting a nonfunctional rearrangement). These data show that GATA3 abundance regulates the recombination propensity at the Tcrb locus and provide new mechanistic insight into the historic immunological conundrum for how Tcrb allelic exclusion is mediated.

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