THE REGULATION OF EXPRESSION OF HISTOCOMPATIBILITY ANTIGENS ON THE CELL-SURFACE - MOLECULAR-GENETIC BASIS

Histocompatibility antigens play a fundamental role in the immune func tions by their polymorphic capture structure for binding exogenous and endogenous peptides and presenting them to the appropriate T and B ce ll receptors. The genetic background of the control of synthesis of th e histocompatibility antigens is very complex including several loci c ontrolling the wide polymorphic variation of class I and class II hist ocompatibility molecules and their regulation of expression, Most sign ificant variability in the presence or absence of histocompatibility a ntigens could be observed during development, differentiation, and act ivation. The tissue-specific expression is influenced by pathological events such as malignant transformation, viral infection and genetic d efectiveness as well. The research in the field of molecular genetics of the MHC in the last decade revealed, upstream of the coding genes o f class I and class II molecules, a very complex regulatory machinery including a series of genes termed enhancer and promoter region. At th e DNA level, various gene boxes and regulatory elements were discovere d, which are activated by the binding of the appropriate histone prote ins, cytokines or hormones responsible for the upregulation and downre gulation of histocompatibility antigen expression. Regulation is mainl y functioning at the transcriptional level, but other factors such as viral proteins, oncogenes, biomolecules, and physical effects take par t, either indirectly or directly affecting the regulatory genes and DN A binding proteins. The increasing knowledge about the regulatory mach inery may lead to the introduction of genetic manipulation, either exp erimental or clinical, with the aim of changing the expression of hist ocompatibility molecules on the cell surface in order to achieve norma l or demanded immune functions.