Expression level of risk genes of MHC class II is a susceptibility factor for autoimmunity: New insights

To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and proliferation of autoantigen-reactive T cells. Moreover, it is well known that increased expression of MHC class II molecules may alter the T cell receptor repertoire during thymic development, and affect the survival and expansion of mature T cells. Many evidences confirmed that the level of both transcriptional and post-transcriptional regulation are involved in the modulation of the expression of MHC class II genes and that both contribute to the predisposition to autoimmune diseases. Here, we aim to focus some of these regulative aspects to better clarify the role of MHC class II genes in predisposition and development of autoimmunity.