Molecular genetics of the Bare lymphocyte syndrome.
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.
Masternak
K
K
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Muhlethaler-Mottet
A
A
Villard
J
J
Peretti
M
M
Reith
W
W
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D051379:Mice; D008967:Molecular Biology; D000071701:Regulatory Factor X Transcription Factors; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors