Ting J P, Wright K L, Chin K C, Brickey W J, Li G
Lineberger Comprehensive Cancer Center and Department of Microbiology-Immunology, University of North Carolina, Chapel Hill 27514, USA.
J Immunol. 1997 Dec 1;159(11):5457-62.
The HLA-DM loci encode the heterodimeric unconventional class II MHC molecules that are coexpressed with conventional class II MHC molecules. DM molecules are essential for the proper formation and function of conventional class II MHC molecules. This report characterizes the DMB promoter both by in vivo footprint and by in vitro functional analysis and reveals a promoter structure similar to that of conventional class II MHC genes. DR-negative mutant cell lines selectively defective in the transcription factor or class II trans-activator (CIITA) were used to reveal a requirement for both these factors in DMB promoter activation. Complementation of defective cell lines with the appropriate transcription factor reconstituted DMB promoter activation. Further analysis with CIITA identified several mutant forms of CIITA that are trans-dominant-negative mutants, i.e., they suppressed DMB promoter activation by transfected and endogenous CIITA. These mutants may be used in abiological setting to down-regulate the function of DM in Ag processing.
HLA - DM基因座编码与传统II类主要组织相容性复合体（MHC）分子共表达的异二聚体非常规II类MHC分子。DM分子对于传统II类MHC分子的正确形成和功能至关重要。本报告通过体内足迹法和体外功能分析对DMB启动子进行了表征，并揭示了一种与传统II类MHC基因相似的启动子结构。利用在转录因子或II类反式激活因子（CIITA）中选择性缺陷的DR阴性突变细胞系，揭示了DMB启动子激活对这两种因子的需求。用适当的转录因子对缺陷细胞系进行互补可重建DMB启动子激活。用CIITA进行的进一步分析鉴定出几种CIITA突变形式，它们是反式显性阴性突变体，即它们抑制转染的和内源性CIITA对DMB启动子的激活。这些突变体可用于非生物环境中下调DM在抗原加工中的功能。
