scholarly journals A T-cell-specific transcriptional enhancer element 3' of C alpha in the human T-cell receptor alpha locus

1989 ◽  
Vol 86 (17) ◽  
pp. 6714-6718 ◽  
Author(s):  
I C Ho ◽  
L H Yang ◽  
G Morle ◽  
J M Leiden
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Simian Virus 40 ◽  
Cell Receptor ◽  
Simian Virus ◽  
Transcriptional Enhancer ◽  
Enhancer Element ◽  
Alpha Chain ◽  
Human T Cell ◽  
Alpha Beta

A transcriptional enhancer element has been identified 4.5 kilobases 3' of C alpha (constant region alpha chain) in the human T-cell receptor (TCR) alpha-chain locus. This enhancer is active on both a TCR V alpha (variable region alpha chain) promoter and the minimal simian virus 40 promotor in TCR alpha/beta Jurkat and EL4 cells but is inactive on a V alpha promoter in human TCR gamma/delta PEER and Molt-13 cells, clone 13 B cells, and HeLa fibroblasts. The enhancer has been localized to a 116-base-pair BstXI/Dra I restriction enzyme fragment, which lacks immunoglobulin octamer and kappa B enhancer motifs but does contain a consensus cAMP-response element (CRE). DNase I footprint analyses demonstrated that the minimal enhancer contains two binding sites for Jurkat nuclear proteins. One of these sites corresponds to the CRE, while the other does not correspond to a known transcriptional enhancer motif. These data support a model in which TCR alpha gene transcription is regulated by a unique set of cis-acting sequences and trans-acting factors, which are differentially active in cells of the TCR alpha/beta lineage. In addition, the TCR alpha enhancer may play a role in activating oncogene expression in T-lymphoblastoid tumors that have previously been shown to display chromosomal translocations into the human TCR alpha locus.

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.

scholarly journals Deletional rearrangement in the human T-cell receptor alpha-chain locus.

1987 ◽  
Vol 84 (23) ◽  
pp. 8608-8612 ◽  
Author(s):  
J. P. de Villartay ◽  
D. Lewis ◽  
R. Hockett ◽  
T. A. Waldmann ◽  
S. J. Korsmeyer ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Chain Locus ◽  
Human T Cell ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

scholarly journals Diversity and structure of human T-cell receptor alpha-chain variable region genes.

1987 ◽  
Vol 84 (19) ◽  
pp. 6884-6888 ◽  
Author(s):  
M. H. Klein ◽  
P. Concannon ◽  
M. Everett ◽  
L. D. Kim ◽  
T. Hunkapiller ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Variable Region ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Human T Cell ◽  
Variable Region Genes ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

scholarly journals T cell receptor alpha chain genes are located on chromosome 14 at 14q11-14q12 in humans.

1985 ◽  
Vol 161 (5) ◽  
pp. 1255-1260 ◽  
Author(s):  
N Caccia ◽  
G A Bruns ◽  
I R Kirsch ◽  
G F Hollis ◽  
V Bertness ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chromosome 14 ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Human T Cell ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

A cDNA clone encoding the alpha chain of the human T cell receptor was used in connection with somatic cell human-rodent hybrids to determine that the genes coding for the alpha chain are located on chromosome 14 in humans. In situ hybridization confirms this result and further localizes these genes to 14q11-14q12 on this chromosome. Since this region of chromosome has been shown to be nonrandomly involved in a number of T cell neoplasias, this assignment raises a number of interesting questions as to the possible involvement of the T cell receptor alpha chain genes in tumorigenesis.

scholarly journals Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor.

1987 ◽  
Vol 6 (11) ◽  
pp. 3307-3312 ◽  
Author(s):  
S. Luria ◽  
G. Gross ◽  
M. Horowitz ◽  
D. Givol
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Alpha Chain ◽  
Human T Cell

scholarly journals In vivo persistence of expanded clones specific for bacterial antigens within the human T cell receptor alpha/beta CD4-8- subset.

1993 ◽  
Vol 177 (6) ◽  
pp. 1763-1771 ◽  
Author(s):  
P Dellabona ◽  
G Casorati ◽  
B Friedli ◽  
L Angman ◽  
F Sallusto ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Resting Cells ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones ◽  
Bacterial Antigens ◽  
Alpha Beta

We analyzed the T cell receptor (TCR) rearrangements of 100 TCR-alpha/beta CD4-CD8- (double negative [DN]) T cell clones from normal individuals. We found that in four out of six donors this subset contains expanded clones that often account for 0.5% and, in one individual, even 7% of all peripheral blood lymphocytes. By combining limiting dilution analysis and N region oligotyping of polymerase chain reaction amplified TCR cDNA, we could measure the clonal size and show that two of these expanded clones remain stable in size for up to 4 yr in peripheral blood. The expanded clones analyzed ex vivo are not cycling and CD45 RAhi ROlo, but express high levels of alpha 4/beta 1 integrins, suggesting that they may have reverted to resting cells after activation. One of these expanded DN clones proliferates in vitro in response to Escherichia coli presented by monocytes cultured in GM-CSF plus IL-4 and kills CD1a+ Molt-4 cells. In contrast to what was found in the alpha/beta DN subset, alpha/beta CD4+ T cell clones specific for a tetanus toxin epitope showed a very small clonal size (< 1 in 10(7)) and could not be reisolated after 2 yr. Taken together, these results indicate that large clonal size and persistence are distinctive features of alpha/beta DN cells specific for bacterial antigens. These cells may use antigen-presenting cells, restriction molecules, and selection routes different from those used by antigen-specific CD4+ T cells.

Identification and functional analysis of the transcriptional enhancer of the human T cell receptor β gene

1991 ◽  
Vol 21 (1) ◽  
pp. 161-166 ◽  
Author(s):  
Haydn M. Prosser ◽  
Richard A. Lake ◽  
David Wotton ◽  
Michael J. Owen
Keyword(s):  
Functional Analysis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Transcriptional Enhancer ◽  
Human T Cell

scholarly journals Sequences and repertoire of human T cell receptor alpha chain variable region genes in mature T lymphocytes.

1986 ◽  
Vol 164 (1) ◽  
pp. 90-103 ◽  
Author(s):  
Y Yoshikai ◽  
N Kimura ◽  
B Toyonaga ◽  
T W Mak
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Common Mechanism ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Human T Cell ◽  
Alpha Gene ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

24 human T cell receptor alpha chain messages have been examined by cDNA sequence analysis and Southern blot. The data indicate that there are approximately 40 alpha chain T cell receptor variable gene segments, which can be divided into 12 families. Comparison of the J gene segments from the cDNAs to previously determined germline J alpha sequences places the number of J alpha gene segments over 21, and indicates their number to be approximately 55. Identical nucleotide sequences in independent isolates of V alpha and J alpha gene segments indicate that hypermutation may not be a common mechanism for the expansion of diversity in these genes, and suggest that the major source of diversity within the alpha chain repertoire is a result of recombinational joinings between germline V alpha and J alpha sequences, combined with imprecise junctional joining. Analysis of the V regions of these alpha chain messages reveals the presence of three domains of hypervariability roughly analogous to the CDR1, CDR2, and CDR3 regions of immunoglobulin.

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