Over the past several years, intensive efforts have been directed to define the pathogenic mechanisms and explore the potential immunotherapy of autoimmune diseases. The advances of molecular genetics and cellular immunology have now permitted select experimental immunotherapy using synthetic peptides, T cell receptor idiotypes and monoclonal antibodies. There remain many obstacles for success. First, the T cell receptor usage of autoreactive T cells in human autoimmune diseases are more heterogeneous than animal models. Clearly, there may not be an oligoclonal derivation of T cells in humans with autoimmune diseases. We foresee that the following studies might contribute to further understand pathogenic mechanisms and design feasible immunotherapy: (1) detailed characterizations of self-antigen specific T cell clones; (2) definition of interactions between MHC molecules and T cell receptors at the molecular level; (3) identification and elution of relevant disease inducing self-peptides complexed with MHC molecules and (4) identification of relevant genes that predispose to autoimmunity.