THE BARE LYMPHOCYTE SYNDROME AND THE REGULATION OF MHC EXPRESSION

• Published in: Annual review of immunology 2001-01, Vol.19 (1), p.331-373
• Main Authors: Reith, Walter, Mach, Bernard
• Format: Article
• Language: English
• Subjects: Animals; bare lymphocyte syndrome; CD4 antigen; CIITA; CIITA protein; Disease Susceptibility; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Gene Expression Regulation - immunology; Genes, MHC Class II; Genes, Recessive; Genetic Complementation Test; Genetic Heterogeneity; histocompatibility antigen HLA; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Humans; Macromolecular Substances; MHC class II deficiency; Mice; Mice, Knockout; Models, Animal; Models, Immunological; Nuclear Proteins; primary immunodeficiency disease; Promoter Regions, Genetic; Protein Subunits; Regulatory Factor X Transcription Factors; RFX; RFX5 protein; RFXANK protein; RFXAP protein; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Trans-Activators - deficiency; Trans-Activators - genetics; Trans-Activators - physiology; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; transcription regulation; Transcriptional Activation
• ISSN: 0732-0582; 1545-3278
• DOI: 10.1146/annurev.immunol.19.1.331

The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting from the absence of major istocompatibility complex class II (MHCII) expression. Considering the central role of MHCII molecules in the development and activation of CD4 + T cells, it is not surprising that the immune system of the patients is severely impaired. BLS is the prototype of a "disease of gene regulation." The affected genes encode RFXANK, RFX5, RFXAP, and CIITA, four regulatory factors that are highly specific and essential for MHCII genes. The first three are subunits of RFX, a trimeric complex that binds to all MHCII promoters. CIITA is a non-DNA-binding coactivator that functions as the master control factor for MHCII expression. The study of RFX and CIITA has made major contributions to our comprehension of the molecular mechanisms controlling MHCII genes and has made this system into a textbook model for the regulation of gene expression.