Molecular genetics of the Bare lymphocyte syndrome
|Published in||Reviews in Immunogenetics. 2000, vol. 2, no. 2, p. 267-282|
|Abstract||Major Histocompatibility Complex class II (MHC-II) molecules play a pivotal role in the adaptive immune system because they direct the development, activation and homeostasis of CD4+ T helper cells. Hereditary defects leading to the absence of MHC-II expression result in a severe autosomal recessive immunodeficiency disease called the Bare Lymphocyte Syndrome (BLS), also referred to as MHC-II deficiency. The genetic lesions responsible for BLS do not lie within the MHC-II locus itself, but reside instead in genes encoding transcription factors controlling MHC-II expression. Mutations in four different MHC-II regulatory genes are known to lead to BLS. These genes encode CIITA, RFXANK, RFX5 and RFXAP. CIITA (Class II Transactivator) is a transcriptional coactivator that functions as a master control factor dictating the cell type specificity, induction and level of MHC-II expression. RFXANK, RFX5 and RFXAP are the three subunits of RFX (regulatory factor X), a DNA-binding complex that binds to a conserved cis-acting sequence, the X box, present in the promoters of all MHC-II genes. Elucidation of the molecular defects underlying BLS has led to major advances in our understanding of the mechanisms regulating expression of MHC-II genes.|
|Keywords||Animals — DNA-Binding Proteins/genetics — Genes, MHC Class II/genetics — Histocompatibility Antigens Class II/genetics — Humans — Mice — Molecular Biology — Severe Combined Immunodeficiency/ genetics — Transcription Factors/genetics|
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