T cell receptor variable beta-gene expression in the normal lung and in active pulmonary sarcoidosis

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.

Download Full-text

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

Molecular and Cellular Biology ◽

10.1128/mcb.10.10.5486-5495.1990 ◽

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.

Download Full-text

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

Molecular and Cellular Biology ◽

10.1128/mcb.13.9.5691 ◽

1993 ◽

Vol 13 (9) ◽

pp. 5691-5701 ◽

Cited By ~ 45

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.

Download Full-text

T-cell receptor V beta gene expression in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3.

Circulation ◽

10.1161/01.cir.89.5.2170 ◽

1994 ◽

Vol 89 (5) ◽

pp. 2170-2175 ◽

Cited By ~ 17

Author(s):

Y Seko ◽

H Yagita ◽

K Okumura ◽

Y Yazaki

Keyword(s):

Gene Expression ◽

T Cell ◽

T Cell Receptor ◽

Acute Myocarditis ◽

Cell Receptor ◽

Coxsackievirus B3 ◽

Infiltrating Cells ◽

Beta Gene

Download Full-text

T-cell receptor V gene expression in HLA-typed Japanese patients with pulmonary sarcoidosis.

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/ajrccm.151.1.7812546 ◽

1995 ◽

Vol 151 (1) ◽

pp. 151-156 ◽

Cited By ~ 20

Author(s):

J Grunewald ◽

M Shigematsu ◽

S Nagai ◽

T Mikuniya ◽

H Wigzell ◽

...

Keyword(s):

Gene Expression ◽

T Cell ◽

T Cell Receptor ◽

Japanese Patients ◽

Cell Receptor ◽

Pulmonary Sarcoidosis ◽

V Gene

Download Full-text

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.

Molecular and Cellular Biology ◽

10.1128/mcb.10.10.5486 ◽

1990 ◽

Vol 10 (10) ◽

pp. 5486-5495 ◽

Cited By ~ 54

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.

Download Full-text

Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v70.6.1933.bloodjournal7061933 ◽

1987 ◽

Vol 70 (6) ◽

pp. 1933-1939

Author(s):

A Tawa ◽

SH Benedict ◽

J Hara ◽

N Hozumi ◽

EW Gelfand

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

T Cell Receptor ◽

Gene Rearrangement ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Cell Receptor ◽

Gene Rearrangements ◽

Gamma Chain ◽

Beta Gene

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.

Download Full-text