Regulation of HLA gene expression

The important role of the Major Histocompatibility Complex (MHC) in the immune response is well known. The development of a high genetic polymorphism led to a well differentiated set of molecules able to interact with a wide range of antigenic peptides and to present them to T cells. Endogenous peptides bound to class I molecules are recognized by cytotoxic CD8+T cells while exogenous peptides bound to class II molecules react with helper CD4+T cells. The distribution of class I and II molecules is different among different cell types. Only a restricted cell subset constitutively expresses class II antigens, while all nucleated cells present class I molecules on their cell surfaces. However, a de novo expression of class II molecules can be induced in many cell types by cytokines treatment. Recent studies have brought attention to the mechanisms at the basis of the tissue-specific and inducible expression of HLA antigens as well as their quantitative regulation. A polymorphism in the promoter region of DQA1 and DQB1 genes has recently been described. The functional importance of these variations has not been well understood, yet. However, various authors reported the different transcription activity of the promoter regions of HLA genes. In the present al-tide the known mechanisms of HLA gene regulation, together with the promoter structure of the class I and II genes and their DNA binding factors will be reviewed. Methods for the quantification of RNA molecules and their application to the HLA genes will be also described.