Characterization of mature and immature Rad LV‐Induced thymic T‐cell lines for tumorigenesis and mhc‐class‐I gene expression

Bashi, Orna; Ehrlich, Rachel

doi:10.1002/ijc.2910610112

Cited by 2 publications

(1 citation statement)

References 20 publications

(13 reference statements)

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“…Additional TAP-transfected cell lines are described in the text. PD 1.1 is a RadLV-induced thymic leukemia expressing high levels of class I antigens (39).…”

Section: Methodsmentioning

confidence: 99%

LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.

Rotem-Yehudar

Groettrup

Soza

et al. 1996

The Journal of Experimental Medicine

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SummaryExpression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the in vivo oncogenicity of this virus. In primary embryonal fibroblasts (H-26) that express a transgenic swine class I antigen (PD 1), Ad12-mediated transformation results in inhibition in transport of newly synthesized class I molecules, as well as significant reduction in transporter associated with antigen presentation (TAP) gene expression. In this report we show that reexpression of TAP molecules either by stable transfection of mouse TAP genes or by infection with recombinant vaccinia viruses expressing human TAP genes, only partially reconstitutes the expression and transport of the class I molecueles. Further analysis of Ad12-transformed cells revealed that the expression of both LMP2 and LMP7, but not of other proteasome complex components, was downregulated, resulting in altered proteolytic activities of the 20S proteasomes. Reconstitution of both TAP and LMP expression resulted in complete restoration of PD1 cell surface expression and enhanced expression of the endogenous H-2D 6 molecules. Despite high expression of TAP, LMP, and class I MHC molecules encoded by recombinant vaccinia viruses, in reconstituted Ad12-transformed cells, efficient transport of H-2 class I molecules could only be achieved by treatment of the cells with ~/-interferon. These data suggest that an additional factor(s) that is interferon-regulated plays a role in the biosynthetic pathway of the class I complex, and that its function is deficient in this cell system. Thus, Ad12 viral transformation appears to suppress the expression of multiple genes that are important for antigen processing and presentation, which allows such transformed cells to escape immune surveillance. This coordinate downregnlation of immune response genes must likely occur through their use of common regulatory elements.

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“…Additional TAP-transfected cell lines are described in the text. PD 1.1 is a RadLV-induced thymic leukemia expressing high levels of class I antigens (39).…”

Section: Methodsmentioning

confidence: 99%

LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.

Rotem-Yehudar

Groettrup

Soza

et al. 1996

The Journal of Experimental Medicine

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Organization and Functional Analysis of the Mouse Transporter Associated with Antigen Processing 2 Promoter

Arons

Kunin

Schechter

et al. 2001

The Journal of Immunology

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In accordance with the key role of MHC class I molecules in the adaptive immune response against viruses, they are expressed by most cells, and their expression can be enhanced by cytokines. The assembly and cell surface expression of class I complexes depend on a continuous peptide supply. The peptides are generated mainly by the proteasome and are transported to the endoplasmic reticulum by a peptide transport pump consisting of two subunits, TAP1 and TAP2. The proteasome low molecular weight polypeptide (2 and 7), as well as TAP (1 and 2) genes, are coordinately regulated and are induced by IFNs. Despite this coordinate regulation, examination of tumors shows that these genes can be discordantly down-regulated. In pursuing a molecular explanation for these observations, we have characterized the mouse TAP2 promoter region and 5′-flanking sequence. We show that the 5′ untranslated regions of TAP2 genes have a characteristic genomic organization that is conserved in both the mouse and the human. The mouse TAP2 promoter belongs to a class of promoters that lack TATA boxes but contain a MED1 (multiple start site element downstream) sequence. Accordingly, transcription is initiated from multiple sites within a 100-nucleotide window. An IFN regulatory factor 1 (IRF1)/IRF2 binding site is located in this region and is involved in both basal and IRF1-induced TAP2 promoter activity. The implication of the extensive differences found among the promoters of class I heavy chain, low molecular weight polypeptide, and TAP genes, all encoding proteins involved in Ag presentation, is discussed.

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Characterization of mature and immature Rad LV‐Induced thymic T‐cell lines for tumorigenesis and mhc‐class‐I gene expression

Cited by 2 publications

References 20 publications

LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.

LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.

Organization and Functional Analysis of the Mouse Transporter Associated with Antigen Processing 2 Promoter

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