Regulation of tissue-specific alternative splicing: exon-specific cis-elements govern the splicing of leukocyte common antigen pre-mRNA.

Streuli, Michel; Saito, Haruo

doi:10.1002/j.1460-2075.1989.tb03439.x

Cited by 144 publications

(108 citation statements)

References 54 publications

(46 reference statements)

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“…cis-Acting sequences and trans-acting factors have been postulated to influence the alternative splicing pattern of CD45. Linker scanning analysis revealed that in exon A three segments (positions 8 -10, 40 -91, and 127-137, total length 198 bp) and in exon C one large segment (positions 16 -137, total length 144 bp) were essential for tissue-specific alternative splicing (46,47). No such segments were found in exon 5, suggesting that splicing of exon 5 is not regulated in a tissue-specific manner (46, 47).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Alternative Splicing of CD45 by Antagonistic Effects of SR Protein Splicing Factors

Dam¹,

Zilch

Wallace

et al. 2000

The Journal of Immunology

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CD45 is a transmembrane glycoprotein possessing tyrosine phosphatase activity, which is involved in cell signaling. CD45 is expressed on the surface of most leukocytes and can be alternatively spliced by the inclusion or skipping of three variable exons (4, 5, and 6 or A, B, and C) to produce up to eight isoforms. In T cells, the splicing pattern of CD45 isoforms changes after activation; naive cells express high m.w. isoforms of CD45 which predominantly express exon A (CD45RA), whereas activated cells lose expression of exon A to form low m.w. isoforms of CD45 including CD45RO. Little is known about the specific factors controlling the switch in CD45 splicing which occurs on activation. In this study, we examined the influence of the SR family of splicing factors, which, like CD45, are expressed in tissue-specific patterns and have been shown to modulate the alternative splicing of a variety of transcripts. We show that specific SR proteins have antagonistic effects on CD45 splicing, leading either to exon inclusion or skipping. Furthermore, we were able to demonstrate specific changes in the SR protein expression pattern during T cell activation.

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Section: Discussionmentioning

confidence: 99%

Regulation of Alternative Splicing of CD45 by Antagonistic Effects of SR Protein Splicing Factors

Dam¹,

Zilch

Wallace

et al. 2000

The Journal of Immunology

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“…NIH 3T3 cells, a MHC class II-negative B7-negative murine fibroblast cell line, were transfected by electroporation with DR7 (t-DR7), B7 (t-B7), or both DR7 and B7 (t-DR7/B7). For each transfection 20 .g of Pvu I-linearized plasmid containing the B7-pLEN construct (8) (a kind gift of California Biotechnology, Mountain View) and/or 20 ug each of the DRa and DRB1*0701 /-chain cDNAs (21) were transfected with 5 ,ug of Pvu I-linearized SV2-Neo-Sp65 plasmid (22). The expression of MHC class II and B7 molecules was assessed using mAbs 9-49 and anti-B7, respectively.…”

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confidence: 99%

Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation.

Gimmi

Freeman

Gribben

et al. 1993

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

500

298

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The maximal T-cell response to its antigen requires presentation of the antigen by a major histocompatibility complex class II molecule as well as the delivery of one or more costimulatory signals provided by the antigenpresenting cell (APC). Although a number of candidate molecules have been identified that are capable of delivering a costimulatory signal, increasing evidence suggests that one such critical pathway involves the interaction of the T-cell surface antigen CD28 with its ligand B7, expressed on APCs.In view of the number of potential costimulatory molecules that might be expressed on the cell surface of APCs, artificial APCs were constructed by stable transfection of NIM 3T3 cells with HLA-DR7, B7, or both. Here, we show that in a human antigen-specific model system, when tetanus toxoid peptide antigen is presented by cells cotransfected with HLA-DR7 and B7, optimal T-cell proliferation and interleukin 2 production result. In contrast, antigen presentation, in the absence of B7 costimulation, results in T-cell clonal anergy. These results demonstrate that it is possible to induce antigen-specific clonal tolerance in human T cells that have been previously sensitized to antigen. The artificial antigen-presenting system provides a useful model for the investigation of the biochemical events involved in the generation of tolerance and for the study of signals necessary to overcome tolerance.The maximal T-cell response to its antigen requires presentation of the antigen by a major histocompatibility complex (MHC) class II molecule and the delivery of one or more costimulatory signals provided by heterotypic adhesion between receptor ligand pairs on the T cell and the antigenpresenting cell (APC) (1-3). Signaling through the T-cell receptor (TCR) complex alone can result in a downregulatory signal for human T-cell growth (4, 5). In vitro systems in the mouse have demonstrated that in the absence of a costimulatory signal, occupancy of the TCR by peptide fragments in the context of MHC class II is capable of inducing a long-lasting antigen-specific unresponsiveness, termed anergy (1, 3, 6). Increasing in vitro evidence in murine and human systems suggests that one such critical costimulatory pathway involves the interaction of the T-cell surface antigen CD28 with its ligand B7 on the APC (7-10). CD28 is constitutively expressed on 95% of resting CD4+ and 50% of CD8+ human T lymphocytes (11,12). After T-cell activation, CTLA4, a second higher-affinity ligand for B7 (13), is expressed and CD28 expression increases. B7 expression is limited to cells capable of presenting antigen, including activated B cells (14), activated monocytes (15), and dendritic cells (16). After T-cell activation, ligation of CD28 by anti-CD28 monoclonal antibody (mAb) or by B7 induces maximal proliferation and interleukin 2 (IL-2) secretion (7,8,17,18). Two recent studies in murine systems suggest that the inhibition of the CD28-B7The publication costs of this article were defrayed in part by page charge payment. This articl...

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“…The small Xba I-Dra III DNA fragment of the mutant CD26 cDNA containing the deletion was substituted for the corresponding DNA fragment of the wild-type CD26 cDNA in the expression vector RcSRa to yield RcSRa-26A3-9 (13). A mixture of RcSRa-26.A&3-9 and pMT-2 (14) providing the dihydrofolate reductase (DHFR) gene was used to transfect a DHFR-deficient CHO cell line, DXB-11, by electroporation (15).…”

mentioning

confidence: 99%

Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV.

Tanaka

Duke‐Cohan

Kameoka

et al. 1994

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

117

106

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Regulation of tissue-specific alternative splicing: exon-specific cis-elements govern the splicing of leukocyte common antigen pre-mRNA.

Abstract: Tissue-specific alternative splicing is an important mechanism for controlling gene expression.

Cited by 144 publications

References 54 publications

Regulation of Alternative Splicing of CD45 by Antagonistic Effects of SR Protein Splicing Factors

Regulation of Alternative Splicing of CD45 by Antagonistic Effects of SR Protein Splicing Factors

Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation.

Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV.

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