Genetic predisposition to autoimmune diseases conferred by the major histocompatibility complex: Utility of animal models

The human immune system has evolved over the centuries due to strong selection pressures caused by various infectious agents. The major players for clearing infection are the genes of major histocompatibility complex (MHC). The MHC region encodes for the most polymorphic genes in human genome, human leukocyte antigen (HLA). A population with diverse HLA class II alleles is able to generate a response to various infections and have a survival advantage. However, the presence of certain class II alleles has been linked to the development of autoimmune diseases. The development of autoimmune diseases, such as rheumatoid arthritis, type I diabetes, multiple sclerosis, or celiac disease is determined by genetic and environmental factors. Among the genetic factors, HLA class II genes confer the highest relative risk to the majority of autoimmune diseases. Thus while the disease-associated HLA class II molecules are efficient in clearing infections, they predispose to autoimmunity.