Lessons from the bare lymphocyte syndrome: molecular mechanisms regulating MHC class II expression

Immunol Rev. 2000 Dec:178:148-65. doi: 10.1034/j.1600-065x.2000.17813.x.


Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the development and maintenance of tol erance. It is thus not surprising that the absence of MHCII expression results in a severe primary immunodeficiency disease (the bare lymphocyte syndrome (BLS)). The genetic defects responsible for BLS do not lie within the MHCII locus, but in genes encoding transcription factors required for MHCII expression. A great deal of our current knowledge about the mechanisms regulating expression of MHCII genes has been derived from the study of BLS. Four different MHCII regulatory genes have been identified. These genes encode RFXANK, RFXS, RFXAP and CIITA. The first three are subunits of RFX, a ubiquitously expressed factor that binds to the promoters of all MHCII genes. RFX binds co-operatively with other factors to form a highly stable multiprotein complex referred to as the MHCII enhanceosome. This enhanceosome serves as a landing pad for the co-activator CIITA, which is recruited via protein-protein interactions CIITA is the master control factor for MHCII expression. The highly regulated expression pattern of CIITA ultimately dictates the cell type specificity, induction and level of MHCII expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Genes, MHC Class II*
  • Genetic Carrier Screening
  • Genetic Complementation Test
  • Genetic Therapy
  • Humans
  • Male
  • Mice
  • Nuclear Proteins*
  • Pregnancy
  • Prenatal Diagnosis
  • Promoter Regions, Genetic
  • Regulatory Factor X Transcription Factors
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / therapy
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • MHC class II transactivator protein
  • Nuclear Proteins
  • RFX5 protein, human
  • RFXANK protein, human
  • RFXAP protein, human
  • Regulatory Factor X Transcription Factors
  • Rfxap protein, mouse
  • Trans-Activators
  • Transcription Factors