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 tolerance. 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, RFX5, 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.