Molecular genetics of the Bare lymphocyte syndrome
Masternak, K.; Muhlethaler-Mottet, A.; Villard, J.; Peretti, M.; Reith, W.
Reviews in Immunogenetics 2(2): 267-282
2000
ISSN/ISBN: 1398-1714 PMID: 11258423 Document Number: 7163
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.
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