Major Histocompatibility Complex–linked Control of Autoimmunity

Although the MHC is a key genetic component in autoimmune disease, our knowledge of the mechanisms by which the molecules encoded within the MHC influence autoimmune processes remains incomplete. Because of the linkage disequilibrium that exists among the class I, II, and III genes within the HLA complex in humans and the homologous MHC complex in rodents, the absolute contribution of the individual loci has been difficult to dissect. However, it is clear from association and linkage studies of autoimmune diseases in humans as well as from various forms of analyses in the mouse and rat for diseases such as spontaneous autoimmune diabetes and experimentally induced encephalomyelitis, arthritis, and thyroiditis, that class II molecules are a primary (but not always the sole) basis of the HLA–MHC association. One area of intense investigation and speculation has been stimulated by the demonstration that particular class II molecules have positive, neutral, or...