Janitz M, Mitchison A, Reiners-Schramm L, Lauster R
Deutsches RheumaForschungsZentrum, Berlin, Germany.
Tissue Antigens. 1997 Feb;49(2):99-106. doi: 10.1111/j.1399-0039.1997.tb02721.x.
The promoter regions of MHC class II genes are characterized by the presence of conserved sequence motifs called S,X and Y boxes, which are crucial for regulation of transcription of these genes. In humans, promoter polymorphism is known to result in differential transcriptional activity at both inter-locus and inter-allelic levels, but it is not yet known how this relates to tissue-specific expression of MHC class II molecules. We sequenced the 5' regulatory regions of alpha and beta genes of I-A and I-E molecules from four mouse haplotypes and found allelic polymorphisms which were mainly confined to the X box. The promoter sequences of I-Ea genes were non-polymorphic. Transfection of four antigen-presenting cell types with promoter-reporter gene constructs revealed that the promoter sequence polymorphisms result in distinct allele- and tissue-specific activity patterns. Mutagenesis experiments in which the X2 box was reshuffled between I-A beta alleles demonstrated that this box contributes to regulation of differential MHC class II expression in the four cell types. The possibility is discussed that tissue-specific MHC class II expression may control differentiation of T-cell subsets.
MHC II类基因的启动子区域的特征是存在称为S、X和Y盒的保守序列基序，这些基序对于调控这些基因的转录至关重要。在人类中，已知启动子多态性会导致基因座间和等位基因间水平的差异转录活性，但尚不清楚这与MHC II类分子的组织特异性表达有何关系。我们对来自四种小鼠单倍型的I-A和I-E分子的α和β基因的5'调控区域进行了测序，发现等位基因多态性主要局限于X盒。I-Ea基因的启动子序列无多态性。用启动子-报告基因构建体转染四种抗原呈递细胞类型，结果表明启动子序列多态性导致了不同的等位基因和组织特异性活性模式。在I-Aβ等位基因之间对X2盒进行改组的诱变实验表明，该盒有助于调控四种细胞类型中MHC II类的差异表达。文中讨论了组织特异性MHC II类表达可能控制T细胞亚群分化的可能性。
