Steimle V, Durand B, Barras E, Zufferey M, Hadam M R, Mach B, Reith W
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Genes Dev. 1995 May 1;9(9):1021-32. doi: 10.1101/gad.9.9.1021.
Regulation of MHC class II gene expression is an essential aspect of the control of the immune response. Primary MHC class II deficiency is a genetically heterogeneous disease of gene regulation that offers the unique opportunity of a genetic approach for the identification of the functionally relevant regulatory genes and factors. Most patients exhibit a characteristic defect in the binding of a nuclear complex, RFX, to the X box motif of MHC class II promoters. Genetic complementation of a B-lymphocyte cell line from such a patient with a cDNA expression library has allowed us to isolate RFX5, the regulatory gene responsible for the MHC class II deficiency. This gene encodes a novel DNA-binding protein that is indeed a subunit of the RFX complex. Mutations in the RFX5 gene have been characterized in two patients. Transfection of the patient's cells with the RFX5 cDNA repairs the binding defect and fully restores expression of all the endogenous MHC class II genes in vivo.
MHC II类基因表达的调控是免疫反应控制的一个重要方面。原发性MHC II类缺陷是一种基因调控的遗传性异质性疾病，它为通过遗传学方法鉴定功能相关的调控基因和因子提供了独特的机会。大多数患者在一种核复合物RFX与MHC II类启动子的X盒基序结合方面表现出特征性缺陷。用cDNA表达文库对来自此类患者的B淋巴细胞系进行基因互补，使我们能够分离出RFX5，即导致MHC II类缺陷的调控基因。该基因编码一种新型DNA结合蛋白，它确实是RFX复合物的一个亚基。已在两名患者中对RFX5基因的突变进行了表征。用RFX5 cDNA转染患者细胞可修复结合缺陷，并在体内完全恢复所有内源性MHC II类基因的表达。
