Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X.
The expression of MHC class II genes is tightly regulated. One form of congenital severe combined immunodeficiency (SCID) is characterized by a regulatory defect that precludes expression of HLA class II genes. B lymphocyte cell lines from such SCID patients provide a tool for identifying putative regulatory proteins that bind to class II gene promoters. We have identified three proteins binding to specific segments of the HLA-DRA promoter, two of which interact to form the predominant DNA-protein complex observed. One of these proteins, defined as an X box binding protein (RF-X), is specifically missing in cells from class II deficient SCID patients. We propose that the molecular defect in this congenital HLA class II regulatory deficiency is a lack of RF-X and that this factor plays an important role in the normal regulation of MHC class II gene expression.
D001402:B-Lymphocytes; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D003850:Deoxyribonuclease I; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000151:congenital / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D003850:Deoxyribonuclease I