Regulation of MHC class II expression, a unique regulatory system identified by the study of a primary immunodeficiency disease.
Major histocompatibility complex class II (MHC-II) molecules are of central importance for adaptive immunity. Defective MHC-II expression causes a severe immunodeficiency disease called bare lymphocyte syndrome (BLS). Studies of the molecular defects underlying BLS have been pivotal for characterization of the regulatory system controlling the transcription of MHC-II genes. The precisely controlled pattern of MHC-II gene expression is achieved by a very peculiar and highly specialized molecular machinery that involves the interplay between ubiquitous DNA-binding transcription factors and a highly unusual, tightly regulated, non-DNA-binding coactivator called the MHC class II transactivator (CIITA). CIITA single handedly coordinates practically all aspects of MHC-II gene regulation and has therefore been dubbed the master controller of MHC-II expression. Several of the unusual features of the MHC-II regulatory system may be a consequence of the fact that CIITA originated from an ancient family of cytoplasmic proteins involved in inflammation and innate immunity. The function of CIITA in transcriptional regulation of MHC-II genes could thus be a recent acquisition by an ancestral protein having a role in an unrelated system.
Krawczyk
M
M
University of Geneva Medical School, CMU, Switzerland.
Reith
W
W
D000818:Animals; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D018448:Models, Immunological; D015534:Trans-Activators; D014157:Transcription Factors
D015534:Trans-Activators; D014157:Transcription Factors