The regulation of expression of histocompatibility antigens on the cell surface; molecular genetic basis.

Histocompatibility antigens play a fundamental role in the immune functions by their polymorphic capture structure for binding exogenous and endogenous peptides and presenting them to the appropriate T and B cell receptors. The genetic background of the control of synthesis of the histocompatibility antigens is very complex including several loci controlling the wide polymorphic variation of class I and class II histocompatibility molecules and their regulation of expression. Most significant variability in the presence or absence of histocompatibility antigens could be observed during development, differentiation, and activation. The tissue-specific expression is influenced by pathological events such as malignant transformation, viral infection and genetic defectiveness as well. The research in the field of molecular genetics of the MHC in the last decade revealed, upstream of the coding genes of class I and class II molecules, a very complex regulatory machinery including a series of genes termed enhancer and promoter region. At the DNA level, various gene boxes and regulatory elements were discovered, which are activated by the binding of the appropriate histone proteins, cytokines or hormones responsible for the upregulation and downregulation of histocompatibility antigen expression. Regulation is mainly functioning at the transcriptional level, but other factors such as viral proteins, oncogenes, biomolecules, and physical effects take part, either indirectly or directly affecting the regulatory genes and DNA binding proteins. The increasing knowledge about the regulatory machinery may lead to the introduction of genetic manipulation, either experimental or clinical, with the aim of changing the expression of histocompatibility molecules on the cell surface in order to achieve normal or demanded immune functions.