共查询到20条相似文献,搜索用时 15 毫秒
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Major histocompatability complex class II (MHCII) molecules are an essential component of the mammalian adaptive immune response. The expression of MHCII genes is regulated by a cell-specific multiprotein complex, termed the MHCII enhanceosome. The heterotrimeric RFX complex is the key DNA-binding component of the MHCII enhanceosome. The RFX complex is comprised of three proteins, RFXB, RFXAP, and RFX5, all of which are required for DNA binding and activation of MHCII gene expression. Static light scattering and chemical cross-linking of the three RFX proteins show that RFXB and RFXAP are monomers and that RFX5 dimerizes through two separate domains. One of these domains, the oligomerization domain, promotes formation of a dimer of dimers of RFX5. In addition, we show that the RFX complex forms a 2:1:1 complex of RFX5.RFXAP.RFXB, which can associate with a further dimer of RFX5 to form a 4:1:1 complex through the oligomerization domain of RFX5. On the basis of these studies, we propose DNA-binding models for the interaction between the RFX complex and the MHCII promoter including a DNA looping model. We also provide direct evidence that the RFX5(L66A) point mutation prevents dimerization of the RFX complexes and propose a model for how this results in a loss of MHCII gene expression. 相似文献
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Yikun Yao Yalong Wang Fuxiang Chen Yin Huang Shu Zhu Qibin Leng Hongyan Wang Yufang Shi Youcun Qian 《Cell research》2012,22(5):836-847
NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection. NLRC5, the largest member of the NLR family, has recently attracted much attention. However, in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways. The in vivo function of NLRC5 remains unknown. Here, we report that NLRC5 is a critical regulator of host defense against intracellular pathogens in vivo. NLRC5 was specifically required for the expression of genes involved in MHC class I antigen presentation. NLRC5-deficient mice showed a profound defect in the expression of MHC class I genes and a concomitant failure to activate L. monocytogenes-specific CD8+ T cell responses, including activation, proliferation and cytotoxicity, and the mutant mice were more susceptible to the pathogen infection. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for pathogen-induced expression of NF-κB-dependent pro-inflammatory genes as well as type I interferon genes. Thus, NLRC5 critically regulates MHC class I antigen presentation to control intracellular pathogen infection. 相似文献
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Peijnenburg A Van Eggermond MC Van den Berg R Sanal O Vossen JM Van den Elsen PJ 《Immunogenetics》1999,49(4):338-345
Patients suffering from major histocompatibility complex (MHC) class II deficiency, a rare primary immunodeficiency, are
characterized by a lack of MHC class II expression which is the result of defects in trans-acting factors. At least four complementation
groups, A, B, C, and D, can be discerned. The gene affected in group C patients is known to be RFX5 and encodes one of the subunits of the multimeric phosphoprotein complex, RFX. In the present study we fused fibroblasts
of a recently identified MHC class II deficiency patient, OSE, with fibroblasts derived from patients representative of each
of the four complementation groups. Transient heterokaryon analysis indicated that OSE belonged to complementation group C.
Furthermore, transfection of wild-type RFX5 cDNA into OSE fibroblasts resulted in restoration of the defect. Mutation analysis revealed that the RFX5 mRNA lacked four nucleotides and that this deletion was the consequence of a G to A transition in a splice acceptor site.
Genomic oligotyping demonstrated that OSE was homozygous for the splice site mutation.
Received: 15 July 1998 / Revised: 3 September 1998 相似文献
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V Kouskoff R M Mantovani S M Candéias A Dorn A Staub B Lisowska-Grospierre C Griscelli C O Benoist D J Mathis 《Journal of immunology (Baltimore, Md. : 1950)》1991,146(9):3197-3204
The X box has been shown in several assay systems to be a critical element of MHC class II gene promoters. Several X box-binding activities have been discovered in nuclear extracts from a variety of cell lines. The critical question is: which of these are responsible for mediating X box function? This report provides a further characterization of NF-X, a highly specific X box-binding activity we described previously. The cell-type distribution, structural features, and binding site characteristics of NF-X are analyzed in detail, to facilitate comparison with other reported activities. Most importantly, the functional relevance of NF-X is assessed by scanning mutagenesis, and the results indicate that this complex is indeed involved in regulating MHC class II gene expression. With these data in mind, the relationship between NF-X and RF-X, an X box-binding activity reported to be absent in patients with severe combined immunodeficiency, is discussed. 相似文献
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Structure and expression of a chicken MHC class I gene 总被引:7,自引:0,他引:7
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P. J. van den Elsen S. J. P. Gobin Marja C. J. A. van Eggermond A. Peijnenburg 《Immunogenetics》1998,48(3):208-221
Major histocompatibility complex (MHC) molecules serve as peptide receptors. These peptides are derived from processed cellular
or extra-cellular antigens. The MHC gene complex encodes two major classes of molecules, MHC class I and class II, whose function
is to present peptides to CD8+ (cytotoxic) and CD4+ (helper) T cells, respectively. The genes encoding both classes of MHC molecules seem to originate from a common ancestral
gene. One of the hallmarks of the MHC is its extensive polymorphism which displays locus and allele-specific characteristics
among the various MHC class I and class II genes. Because of its central role in immunosurveillance and in various disease
states, the MHC is one of the best studied genetic systems. This review addresses several aspects of MHC class I and class
II gene regulation in human and in particular, the contribution to the constitutive and cytokine-induced expression of MHC
class I and II genes of MHC class-specific regulatory elements and regulatory elements which apparently are shared by the
promoters of MHC class I and class II genes.
Received: 12 January 1998 相似文献
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A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes. 总被引:4,自引:0,他引:4 下载免费PDF全文
U Henseling W Schmidt H R Sch?ler P Gruss A K Hatzopoulos 《Molecular and cellular biology》1990,10(8):4100-4109
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Biswas A Meissner TB Kawai T Kobayashi KS 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(2):516-520
MHC class I and class II are crucial for the adaptive immune system. Although regulation of MHC class II expression by CIITA has long been recognized, the mechanism of MHC class I transactivation has been largely unknown until the recent discovery of NLRC5/class I transactivator. In this study, we show using Nlrc5-deficient mice that NLRC5 is required for both constitutive and inducible MHC class I expression. Loss of Nlrc5 resulted in severe reduction in the expression of MHC class I and related genes such as β(2)-microglobulin, Tap1, or Lmp2, but did not affect MHC class II levels. IFN-γ stimulation could not overcome the impaired MHC class I expression in Nlrc5-deficient cells. Upon infection with Listeria monocyogenes, Nlrc5-deficient mice displayed impaired CD8(+) T cell activation, accompanied with increased bacterial loads. These findings illustrate critical roles of NLRC5/class I transactivator in MHC class I gene regulation and host defense by CD8(+) T cell responses. 相似文献