Genetics and Autoimmunity: HLA and MHC Genes

The genes of the major histocompatibility complex (MHC) plays important role in adaptive immunity. From various in vivo and in vitro studies, it has become clear that MHC and non-MHC genetic components are common elements for various autoimmune diseases and their corresponding animal models. The MHC region encodes for polymorphic human leukocyte antigen (HLA) molecules that are critical for differentiating self from nonself. Mature T cells recognize foreign antigen when it is presented in the context of self-MHC. The loss of self-tolerance of the immune system against the body's own tissues or antigens leads to autoimmunity. The development of autoimmune diseases, such as rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS) or myasthenia gravis (MG) is determined by both genetic and nongenetic factors. Among the genetics factors, the MHC region is known to be the most important. Within this region, certain HLA class II genes confer the strongest susceptibility to the majority of MHC associated disorders.