Differential expression of porcine major histocompatibility DNA sequences introduced into mouse L cells.

Satz, M. L.; Singer, Dinah S.

doi:10.1128/mcb.3.11.2006

Cited by 11 publications

(4 citation statements)

References 41 publications

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“…This active negative regulation allows for rapid increases in transcription in response to immunomodulators or various conditions of stress. Indeed, numerous examples exist in which MHC class I expression increases in response to these situations, including treatment with interferons, tumor necrosis factor, or alcohol (23)(24)(25)(26).…”

Section: Resultsmentioning

confidence: 99%

A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

Weissman¹,

Singer²

1991

Mol. Cell. Biol.

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A novel regulatory element which contributes to the regulation of quantitative, tissue-specific differences in gene expression has been found between -771 and -676 bp upstream of the major histocompatibility complex (MHC) class I gene, PD1. Molecular dissection of this element reveals the presence of two overlapping functional activities: an enhancer and a silencer. Distinct nuclear factors bind to the overlapping enhancer and silencer DNA sequence elements within the regulatory domain. The levels of factors binding the silencer DNA sequence in different cell types are inversely related to levels of class I expression; in contrast, factors binding the enhancer DNA sequence can be detected in all cells. In cultured cell lines, inhibition of protein synthesis leads to the rapid loss of silencer complexes, with a concomitant increase in both enhancer complexes and MHC class I RNA. From these data, we conclude that a labile silencer factor competes with a constitutively expressed, stable enhancer factor for overlapping DNA-binding sites; the relative abundance of the silencer factor contributes to establishing steady-state levels of MHC class I gene expression.The immune responses of all vertebrate species are mediated by molecules encoded within the major histocompatibility complex (MHC) (19). The MHC class I molecules, which serve as the targets of cellular immune responses and allograft rejection, are receptors for peptide antigens (3). These molecules are transmembrane glycoproteins consisting of a polymorphic heavy chain of 42 to 45 kDa and a nonpolymorphic light chain (P2-microglobulin) of 12 kDa.Consistent with their pivotal role in immune surveillance, the class I molecules are expressed on nearly all somatic tissues (28). However, their level of expression varies markedly among the tissues. The highest levels of cell surface expression of class I antigens occur in the lymphoid tissues: lymph node, peripheral blood lymphocytes, and spleen. Markedly lower levels are found on other somatic tissues, such as kidney and liver; there is little detectable cell surface class I antigen expression on germ line tissue or brain (28). In general, these differences reflect tissue-specific regulation of gene expression.Analysis of the 5' flanking regions of a number of class I genes has revealed the presence of a series of DNA elements capable of participating in the regulation of class I gene expression (Fig. 1A). Among these is a major enhancer, enhancer A, located at bp -180 to -170, which overlaps an interferon response element (15,20,27). A functional enhancer A is necessary for optimal expression of the downstream class I gene (13,15,18). A variety of trans-acting factors which bind to enhancer A have been identified, and their genes have been cloned (17, 21). These factors act as inducers of class I expression. Thus, KbF1 and RIIBP, both of which bind enhancer A, are associated with high levels of expression. Factors which bind specifically to the interferon response element and are induced by interferon have also b...

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Section: Resultsmentioning

confidence: 99%

A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

Weissman¹,

Singer²

1991

Mol. Cell. Biol.

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“…One reason for the lack of lysis could have been the lower level of expression of the hybrid molecules by the L cell transfectants (Table II). To address this possibility, L cell transfectants were cultured for 24 h with IFN-3,, which increases MHC expression in transfected L cells (20). However, even under conditions in which the levels of expression of hybrid H-2 were almost equivalent (>90% of control) to the L cells transfected with the native molecule, no lysis was detected by serological analysis (Table III).…”

Section: Examination Of Polymorphic Determinants Using Ctl Derived Acmentioning

confidence: 99%

Allospecific cytolytic T lymphocytes recognize conformational determinants on hybrid mouse transplantation antigens.

Bluestone¹,

Foo²,

Allen³

et al. 1985

The Journal of Experimental Medicine

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Alloreactive cytolytic T cell (CTL) lines and clones have been used to identify the sites of polymorphism of antigens of the major histocompatibility complex (MHC). Specific CTL were generated against wild-type H-2b products by cells from H-2b mutant mice that had one or a few amino acid changes in either the alpha 1 or alpha 2 domains of the Kb or Db class I molecules. These CTL populations, which might be expected to react with determinants expressed on single MHC domains, were examined for lytic activity on L cells expressing newly constructed hybrid class I molecules. Transformed cell lines expressing native class I molecules or hybrid class I molecules in which the alpha 1 and alpha 2 domains of H-2Kb had been substituted by those domains of H-2Db were lysed by H-2Db-specific CTL. Similarly, all H-2Kb-specific CTL recognized hybrid molecules in which the alpha 1 and alpha 2 domains of H-2Kb were inserted into the H-2Db molecule. In contrast, exchange of the alpha 1 domains of H-2Kb and H-2Db resulted in a total loss of recognition by Kb and Db-specific CTL. These results suggest that the allodeterminants recognized by H-2 mutant CTL are influenced by interactions between the alpha 1 and alpha 2 domains, findings similar to those seen using conventional alloreactive T cells (11). These results were compared to the binding of alloreactive mAbs, including 5 new mAbs specific for the Kb molecules. Finally, it was shown that primary and secondary CTL responses could be generated by direct sensitization against hybrid class I molecules, demonstrating that these molecules express neoantigenic determinants recognized by alloreactive CTL.

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“…It has been indicated that IFNs increase MHC class I gene expression by acting on sequences within or in close proximity to the genes, since human and porcine MHC class I genes introduced into mouse cells increase their expression when treated with IFNs (25,27,39). Consistent with this assumption, Vogel et al (34) reported that promoter activity of a mouse class I gene is upregulated by IFNs via a 350-base-pair (bp) 5' flanking sequence.…”

mentioning

confidence: 99%

Interferons increase transcription of a major histocompatibility class I gene via a 5' interferon consensus sequence.

Sakai¹,

Miyazaki²,

Appella³

et al. 1987

Mol. Cell. Biol.

100

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Interferons (IFNs) augment expression of major histocompatibility class I genes in many cells. To study the effect of IFNs on transcription of class I genes, we prepared and tested activity of chloramphenicol acetyltransferase (CAT) hybrid genes in which the cat gene is under the control of the 5' flanking region of the murine H-2Ld gene. NIH 3T3 cells transiently transfected with a cat construct having the sequence from position -210 to -134 showed a four-to fivefold increase in CAT activity when treated with IFN-at/,. This sequence contains the IFN consensus sequence (ICS) shared among IFN-inducible genes, as well as the class I regulatory element (CRE) that controls up and down regulation of class I gene expression. To determine the precise sequence requirement for the IFN action, the ICS and CRE were independently placed upstream of the class I or a heterologous simian virus 40 promoter, and CAT activity was tested. The ICS, but not the CRE, enhanced activity of both promoters by about twofold upon exposure to IFN-a/1, although greater responses were noted when the ICS and CRE were combined. These results demonstrate that the ICS alone is capable of enhancing promoter activity in response to IFN-a/d treatment and that the CRE exerts a synergistic effect. Further, we show that the ICS functions as an inducible enhancer since it acts regardless of its orientation and distance in the simian virus 40 promoter.

show abstract

Differential expression of porcine major histocompatibility DNA sequences introduced into mouse L cells.

Cited by 11 publications

References 41 publications

A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

Allospecific cytolytic T lymphocytes recognize conformational determinants on hybrid mouse transplantation antigens.

Interferons increase transcription of a major histocompatibility class I gene via a 5' interferon consensus sequence.

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