Dealing with the adaptive immune system during de novo evolution of genes from intergenic sequences

Background: The adaptive immune system of vertebrates has an extraordinary potential to sense and neutralize foreign antigens entering the body. De novo evolution of genes implies that the genome itself expresses novel antigens from intergenic sequences which could cause a problem with this immune system. Peptides from these novel proteins could be presented by the major histocompatibility complex (MHC) receptors to the cell surface and would be recognized as foreign. The respective cells would then be attacked and destroyed, or would cause inflammatory responses. Hence, de novo expressed peptides have to be introduced to the immune system as being self-peptides to avoid such autoimmune reactions. The regulation of the distinction between self and non-self starts during embryonic development, but continues late into adulthood. It is mostly mediated by specialized cells in the thymus, but can also be conveyed in peripheral tissues, such as the lymph nodes and the spleen. The self-antigen...