Protein kinase C‐activating phorbol esters augment expression of T cell receptor genes

Isakov, Noah; Theofilopoulos, Argyrios N.; Dixon, Frank J.

doi:10.1002/eji.1830170611

Cited by 18 publications

(11 citation statements)

References 49 publications

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“…Previous studies have shown that PKC stimulation may lead to increased TCR mRNA levels, but it has been unclear whether every factor capable of stimulating T cell PKC could achieve this (9,10). Furthermore, studies have variously demonstrated either that increased TCRBV transcription only occurs in some Ag-stimulated T cells or conversely, that all T cells exhibit this phenomenon in an active immune lesion (16,17).…”

Section: Discussionmentioning

confidence: 99%

Antigen Triggering Selectively Increases TCRBV Gene Transcription

Lennon

Sillibourne

Furrie

et al. 2000

The Journal of Immunology

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When the TCR binds Ag it is phosphorylated, internalized, and degraded. We wished to examine whether this process was accompanied by a specific concomitant increase in TCR mRNA levels. To do this, PBMC and a T cell clone were cultured with a series of superantigens and an alloantigen. Only T cells specifically responding to an antigenic stimulus had increased levels of TCR β-chain variable (TCRBV)-specific mRNA. This response was apparent after 48 h, peaked around 72 h, and was still elevated after 7 days. Increased gene transcription appeared to be driven solely by Ag as specific Ag depletion prevented culture supernatants transferring this effect. The level of TCRBV mRNA elevation was not influenced by the stimulating Ag, but appeared dependent on the gene encoding the stimulated TCR. Reporter gene assays, using cloned TCRBV gene promoters, confirmed both that TCR gene transcription rises after stimulation and that basal and stimulated levels of TCR transcription vary between different TCRBV genes. These data conclusively demonstrate that there is no direct relationship between TCRBV mRNA and T cell number, and that future repertoire studies must take both factors into account.

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Section: Discussionmentioning

confidence: 99%

Antigen Triggering Selectively Increases TCRBV Gene Transcription

Lennon

Sillibourne

Furrie

et al. 2000

The Journal of Immunology

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“…The similarity of the Via decanucleotide to elements that contribute to cAMP responsiveness (25) and phorbol ester inducibility (7,35) suggests that a protein kinase may be involved in the generation of tissuespecific factors that control V13 transcription. The ability of phorbol esters to augment f-chain expression in EL4 cells (36) have not yet been identified within the P-chain locus, and the activity of V1, promoters independent of such elements has not been tested. Interestingly, two separate immunoglobulin gene promoters in a tandem array can be transcriptionally active in an enhancer-dependent fashion when transfected into B cells (40).…”

Section: Methodsmentioning

confidence: 99%

A conserved sequence in the T-cell receptor beta-chain promoter region.

Anderson

Chou

Loh

1988

Proc. Natl. Acad. Sci. U.S.A.

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The antigen-specific receptors of T and B lymphocytes are distinct, though structurally related, molecules. During development, lymphoid cells assemble functional variable (V) region genes for each receptor chain from separate multimember gene families by somatic DNA rearrangements of individual germ-line segments. Transcription may play a role in regulating the tissue and stage specificity of these rearrangements by controlling the accessibility of germ-line loci to the recombinational machinery. Immunoglobulin Vregion genes are transcribed from tissue-specific promoters that have been well characterized. We report here the characterization of 14 T-cell receptor a-chain V-region gene promoters. Sequence analysis indicates that these promoters do not contain the conserved octamer that is located upstream of all immunoglobulin genes. However, a unique decanucleotide sequence, not present in immunoglobulin genes, is conserved in the promoter region of murine and human V.3 genes. We identify this sequence as a potential regulatory element, based on its position, conservation, and sequence homology to sites known to bind transcription-activating factors. The possibility that the distinct structures of immunoglobulin and T-cell receptor gene promoters may contribute to the tissue-specific rearrangement and expression of receptor gene families is discussed.The tissue-and stage-specific expression of appropriate antigen receptors is critical to lymphocyte function. Mature T cells, which recognize antigen in the context of major histocompatibility complex products, express a cell-surface receptor comprised of disulfide-linked a and P chains. In contrast, B-cell receptors are immunoglobulin molecules consisting of heavy (H) and either K or A light (L) chains. Each of these chains contains an amino-terminal variable (V) region and a carboxyl-terminal constant (C) region. During lymphocyte differentiation, germ-line V, diversity (D), and joining (J) gene segments are somatically recombined to form the V-region genes of each receptor chain (1,2). Assembly of functional immunoglobulin V-region genes is limited to precursor B cells, whereas functional T-cell receptor (TCR) V-region genes are assembled only in developing T cells. Studies on the recombination of transfected substrates, however, suggest that a common "recombinase" may mediate the assembly of all immunoglobulin and TCR V-region gene segments (3). One model to explain the specificity of rearrangement proposes that the accessibility of various gene segments to the common recombinase is modulated differently in each cell type (4). This accessibility is reflected in the nuclease sensitivity and often the transcriptional activity of the target segment. Although the precise relationship between transcription and accessibility is unclear, recent evidence suggests that transcription may be a prerequisite of recombinational activation (5). Thus, specific DNA sites and trans-acting factors that activate tissue-specific transcription may control locus accessibility ...

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“…Recognition of antigen-class II complexes by specific T-cell antigen receptors (TCRs) is an absolute prerequisite for an antigen to be capable of driving a T-cell response. One consequence of T-cell antigen receptor triggering is the downregulation of surface TCR molecules and the upregulation of TCR messenger ribonucleic acid (mRNA) transcript numbers [18,19]. If TCR triggering occurs in sarcoidosis, it would be expected that T-cells from active disease sites would exhibit the appropriate surface and mRNA changes.…”

Section: T-cell Triggeringmentioning

confidence: 99%