Transcription factor NF-kappaB regulates inducible CD83 gene expression in activated T lymphocytes.
The immunoglobulin superfamily member CD83 is expressed on the surface of mature dendritic cells that present processed antigens to T lymphocytes. In addition, T cells acquire CD83 expression following mitogenic stimulation in vitro. Here we report two lines of evidence demonstrating that this inducible lymphocyte response is genetically programmed by transcription factor NF-kappaB and contingent upon proteolytic breakdown of its cytoplasmic inhibitor IkappaBalpha. First, signal-dependent induction of CD83 mRNA expression is blocked in both transformed and primary T cells harboring a degradation-resistant mutant of IkappaBalpha that constitutively represses NF-kappaB. Second, as revealed in gel retardation assays, the IkappaBalpha constitutive repressor prevents the inducible interaction of NF-kappaB with consensus recognition sites identified in the CD83 promoter. Given that IkappaBalpha is functionally coupled to the T-cell antigen receptor, these findings suggest that the downstream transcription unit for CD83 is triggered by NF-kappaB during an adaptive immune response.
McKinsey
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TA
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 802 Rudolph Light Hall, Nashville, TN 37232-0295, USA.
Chu
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Tedder
T F
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Ballard
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D015703:Antigens, CD; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D006801:Humans; D020672:I-kappa B Proteins; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000302:isolation & purification; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D000097802:CD83 Antigen; C000606204:NFKBIA protein, human