The ability to discriminate between self and nonself antigens is vital to the functioning of the immune system as a specific defense against invading microorganisms. Failure of the immune system to "tolerate" self tissues can result in pathological autoimmune states leading to debilitating illness and sometimes death. The induction of autoimmunity involves genetic and environmental factors that have focused the attention of researchers on the trimolecular complex formed by major histocompatibility complex molecules, antigen, and T cell receptors. Detailed molecular characterization of these components points to potential strategies for disease intervention.