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抗原呈递的转录调控。

Transcriptional regulation of antigen presentation.

作者信息

van den Elsen Peter J, Holling Tjadine M, Kuipers Hedwich F, van der Stoep Nienke

机构信息

Department of Immunohematology and Blood Transfusion, Building 1, E3-Q, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

出版信息

Curr Opin Immunol. 2004 Feb;16(1):67-75. doi: 10.1016/j.coi.2003.11.015.

Abstract

MHC class I and class II molecules play essential roles in the adaptive immune response by virtue of their ability to present peptides to T lymphocytes. Given their central role in adaptive immunity, the genes encoding these peptide-presenting molecules are regulated in a tight fashion to meet with local requirements for an adequate immune response. In contrast to MHC class I gene products, which are expressed on almost all nucleated cells, constitutive expression of MHC class II molecules is found only in specialized antigen-presenting cells of the immune system. Expression of both classes of MHC molecules can be induced by immune regulators and upon cell activation. A set of conserved cis-acting regulatory promoter elements mediate the transcription of MHC class I and beta2-microglobulin genes. Of these regulatory elements, the promoters of MHC class II and accessory genes also have the SXY module. The MHC class II transactivator (CIITA) is essential for the activation of MHC class II promoters, and it functions through protein-protein interactions with regulatory factors bound to the SXY module. Given the central role of CIITA in these regulatory processes, it is of interest to identify the DNA-binding factors and co-activators that assemble on CIITA promoters in a cell-type-specific fashion. Accordingly, recent studies include investigations into chromatin remodeling and epigenetic control mechanisms that modulate cell-type-specific transcriptional regulation of genes involved in antigen presentation.

摘要

MHC I类和II类分子通过向T淋巴细胞呈递肽段的能力,在适应性免疫反应中发挥着至关重要的作用。鉴于它们在适应性免疫中的核心作用,编码这些肽呈递分子的基因受到严格调控,以满足局部对充分免疫反应的需求。与几乎在所有有核细胞上都有表达的MHC I类基因产物不同,MHC II类分子的组成性表达仅在免疫系统的特定抗原呈递细胞中发现。两类MHC分子的表达均可由免疫调节因子以及细胞活化诱导。一组保守的顺式作用调控启动子元件介导MHC I类和β2-微球蛋白基因的转录。在这些调控元件中,MHC II类基因和辅助基因的启动子也具有SXY模块。MHC II类反式激活因子(CIITA)对于MHC II类启动子的激活至关重要,它通过与结合在SXY模块上的调控因子进行蛋白质-蛋白质相互作用来发挥功能。鉴于CIITA在这些调控过程中的核心作用,确定以细胞类型特异性方式聚集在CIITA启动子上的DNA结合因子和共激活因子是很有意义的。因此,最近的研究包括对染色质重塑和表观遗传控制机制的研究,这些机制可调节参与抗原呈递的基因的细胞类型特异性转录调控。

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