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At least 379 records · Page 21Linked to original sources
PubMed1998

Regulation of major histocompatibility (MHC) class II human leukocyte antigen-DR alpha gene expression in thyrocytes by single strand binding protein-1, a transcription factor that also regulates thyrotropin receptor and MHC class I gene expression.

The single strand binding protein (SSBP-1) is a positive regulator of TSH receptor gene expression and binds to an element with a GXXXXG motif. The S box of the mouse major histocompatibility class II gene has multiple GXXXXG motifs and can also bind SSBP-1. The S box is one of four highly conserved elements on the 5'-flanking region of class II genes that are necessary for interferon-gamma (IFNgamma) to overcome the normally suppressed state of the gene and induce aberrant class II expression. In this report we show that SSBP-1, when overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte antigen (HLA)-DR alpha class II gene expression, as is IFNgamma or the class II trans-activator (CIITA). This is evidenced by increased exogenous promoter activity, increased endogenous RNA levels, and increased endogenous antigen expression after transfecting full-length SSBP-1 complementary DNA together with a HLA-DR alpha promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid cells whose endogenous SSBP-1 levels are low. IFNgamma reverses the ability of TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection does not cause any increase in IFNgamma-induced exogenous promoter activity, transfection of SSBP-1 and CIITA additively increases endogenous class II RNA levels to levels measured in cells treated with IFNgamma. Further, competition studies show that SSBP-1 binding is necessary for formation of the double strand protein/DNA complexes that are seen in electrophoretic mobility shift assays when the class II 5'-flanking region is incubated with extracts from IFNgamma-treated FRTL-5 cells and that have been previously associated with IFNgamma-induced aberrant class II expression. These data suggest that SSBP-1 is involved in the action of IFNgamma to overcome the normally suppressed state of the class II gene; it functions together with CIITA, whose expression is independently increased by IFNgamma. The effect of SSBP-1 as a positive regulator of class II promoter activity is lost in cells maintained without TSH, in which endogenous SSBP-1 RNA levels are already high in the absence of aberrant class II gene expression. These data suggest that high levels of endogenous SSBP-1 are insufficient to cause aberrant class II expression, but, rather, TSH or IFNgamma treatment additionally modulates the cell, albeit differently, such that transfected or endogenous SSBP-1, respectively, can express its positive regulatory activity. The effect of TSH is consistent with reports indicating that TSH enhances the ability of IFNgamma to increase class II gene expression despite the fact IFNgamma increases endogenous SSBP-1 to only the same levels as in cells untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost when GXXXXG motifs, which exist on both the coding and noncoding strands of the S box, are mutated. Consistent with this, mutation and oligonucleotide competition studies show that GXXXXG motifs are necessary for either strand of the S box to bind protein/DNA complexes containing SSBP-1 in FRTL-5 cell extracts or to bind to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either strand of the HLA-DR alpha S box are functionally distinct. We conclude from these data that the positive regulatory action of SSBP-1 on class II gene expression involves GXXXXG motifs on each strand of the highly conserved S box of the class II 5'-flanking region. As SSBP-1 is modulated by IFNgamma and is involved in class I and TSH receptor as well as class II gene expression in FRTL-5 cells, the sum of the data supports the hypotheses that common transcription factors regulate all three genes, and their altered activities may contribute to the development of autoimmunity.

Animals↗
PubMed1999

Ethanol impairs major histocompatibility complex (MHC) class II molecule-mediated but not MHC class I molecule-mediated T cell response in alcohol-consuming mice.

The goal of this study was to determine whether alcohol affects alloantigen-induced proliferative and cytolytic activity of T cells in mice, and whether the altered immune response was in part due to a defect of IL-2 activity. The ability of spleen cells from individual alcohol-consuming C57BL/6 mice to generate allo-specific mixed lymphocyte response (MLR) and cytotoxic T lymphocyte (CTL) was compared to that of mice fed on an isocaloric maltose diet and regular diet. Allospecific MLR and CTL were generated by sensitizing spleen cells of C57BL/6 mice against spleen cells from BALB/c mice, and the allo-specific CTL activity was determined by the ability of the CTL to kill 51Cr-labeled P815 mastocytoma target cells. Our results showed that the allo-specific MLR of the responder cells from alcohol-consuming mice was significantly reduced (40% reduction, p<0.0 1), and the addition of exogenous interleukin 2 (IL-2) could not reverse the suppression of MLR induced by ethanol. However, our results clearly showed that ethanol has little suppressive effect on allo-reactive CTL of alcohol-consuming mice as compared to the alloreactivity of the control mice (P>0.05). Finally, we also demonstrated that ethanol did not impair the alloantigen-induced IL-2 production in the mixed lymphocyte cultures (P>0.1).

Animals↗
PubMed2002

[Selection for disease resistance in domestic ruminants and swine by indicator traits as well as marker and causal genes--a review. Part 1: Short introduction to immunogenetics of MHC and non-MHC genes and special immunogenetics of cattle and swine].

The introduction deals with immunogenetic investigations on the field of life-stock. The main chapter is outlined as a tabular overview of current opportunities of the application of indicator traits as well as marker and causal genes in breeding for disease resistance in cattle, sheep, goats and swine. In the discussion of the second part, emphasis was layed on diseases of small ruminants in central and western Europe. Indicator traits are discussed with respect of their advantages and disadvantages. The rigorous selection of specific traits is connected with an increase of the number of homozygotes. In contrary, pathogens do undergo mutations, thus escaping the host's immune system. Out of this point of view it is advisable, to set on selection very cautiously. The role of technologies of modern immunogenetics is pointed out in respect of constructing disease resistant animals.

Animals↗
PubMed1992

Major histocompatibility complex (MHC)-encoded HAM2 is necessary for antigenic peptide loading onto class I MHC molecules.

The mutant murine lymphoma cell line RMA-S is unable to present endogenous antigens due to its inability to efficiently assemble class I major histocompatibility complex molecules and antigenic peptides. Therefore, it has been suggested that RMA-S cells are defective either in peptide generation or in peptide transport into the endoplasmic reticulum, where class I major histocompatibility complex molecule assembly is believed to occur. As proteasomes and the putative peptide transporters HAM1 and HAM2 have been implicated in class I antigen processing, we have investigated their expression in RMA-S and its wild-type counterpart RMA. Both proteasomes and HAM1 proteins are expressed at similar levels and show identical subcellular distributions in the two cell lines. However, only one copy of the HAM2 gene is present in RMA-S cells, and it contains a point mutation that leads to a premature stop codon. Thus, the HAM2 protein is absent from RMA-S cells. These data demonstrate that HAM2 is essential for peptide loading onto class I molecules.

Amino Acid Sequence↗
PubMed1989

Study on the origin of major histocompatibility complex (MHC) genes in recombinant mouse strains by detection of polymorphic variants of MHC class III gene, complement C4.

In recombinant mouse strains the elements of the major histocompatibility complex gene cluster are composed of those of the parental strains. The origin of elements except the S region was previously determined by immunological and biochemical typing methods. For determination of the origin of the S region and the possible location of the recombination event around the S region, Southern blot analysis was performed. By the detection of genetic polymorphic patterns of complement C4 gene in 2 of the 5 recombinant strains the recombination was localized down-stream of the C4 gene and before the D gene region.

Animals↗
PubMed1988

Recombinant human IFN-gamma, but not IFN-alpha or IFN-beta, enhances MHC- and non-MHC-encoded glycoproteins by a protein synthesis-dependent mechanism.

Despite quantitative as well as qualitative differences, all three types of IFN (IFN-alpha, IFN-beta, and IFN-gamma) modulate the synthesis as well as the expression of class I and class II histocompatibility Ag and a melanoma-associated Ag located in the plasma membrane as well as the cytoplasm of human melanoma cells. By employing inhibitors of RNA and protein synthesis it was demonstrated that IFN-alpha and -beta increase the expression of histocompatibility products and this tumor-associated Ag by a process not requiring new protein synthesis. In contrast, IFN-gamma does require de novo protein synthesis for its modulatory activity. Thus, it appears that IFN might trigger various adaptive functions in different cell lineages by inducing at least two separate sets of responses specific for either IFN-alpha and -beta or IFN-gamma. Because the induction requirements for (2'-5')-oligoadenylate synthetase as well as for the development of a cellular antiviral state by different IFN also display a similar protein synthesis dependence pattern, the present results suggest that a similar set of cellular mediators may be involved in the modulation of antigenic expression by IFN-gamma in human melanoma cells.

Antigens, Neoplasm↗