Regulation of the expression of mouse TAP-associated glycoprotein (tapasin) by cytokines.
The expression of antigen presenting MHC class I molecules can be enhanced through cytokines, e.g. upon infection with bacteria or viruses, either directly by enhancing class I gene transcription or by increasing the amounts of accessory proteins of the loading complex. Tapasin plays a significant role in the peptide loading of class I molecules. Here, we describe recognition motifs of cytokine inducible transcription factors in the promoter region of the mouse tapasin gene, most of them clustered within the 140 base pairs upstream of the start codon. Tapasin mRNA was strongly induced in vivo after infection with the facultatively intracellular bacterium Listeria monocytogenes in an IFN-gamma-dependent fashion. Accordingly, both tapasin mRNA and protein were strongly induced in a time and dose dependent manner in embryonic fibroblasts treated with the cytokines IFN-gamma and IFN-beta, and weakly induced after treatment with TNF-alpha. Co-stimulation of tapasin by TNF-alpha and IFN-gamma resulted in a weak synergistic effect. Using fibroblasts either lacking IRF-1 or inhibited in protein synthesis we show that secondary transcription factors are necessary for a maximal stimulation of tapasin expression upon IFN-gamma stimulation. The sequential induction of TAP1, LMP2, and tapasin before the stimulated expression of class I heavy chain is discussed.
Abarca-Heidemann
Karin
K
Abteilung für Zellgenetik, Institut für Genetik, Universität zu Köln, Germany.
Friederichs
Sonja
S
Klamp
Thorsten
T
Boehm
Ulrich
U
Guethlein
Lisbeth A
LA
Ortmann
Bodo
B
D000818:Animals; D017920:Antiporters / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008088:Listeriosis / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D015533:Transcriptional Activation / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017920:Antiporters; D016207:Cytokines; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D007136:Immunoglobulins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C107762:tapasin; D016899:Interferon-beta; D007371:Interferon-gamma