Protection against microbial attack or invasion is a fundamental function of the immune system. Crucial to this function is the ability to distinguish "self" from the invading organism, and tolerate "self" while removing "non-self". The ability to distinguish self from non-self is not inherent in the immune system, but rather is acquired and continuously maintained. Unfortunately, the mechanisms maintaining self-tolerance are not perfect, and at times break down. In these instances an autoimmune disease results. T cells initiate normal immune responses, and it is now clear that T cells can also initiate pathologic immune responses. In animal models, T cells produce diseases resembling rheumatoid arthritis (RA) (1-3), systemic lupus erythematosus (4-6) and progressive systemic sclerosis (7,8). It is likely that T cells participate in human autoimmune diseases as well. The molecular basis of T cell antigen recognition has been clarified over the past decade. These advances now allow direct examination of the T cell receptor (TCR) molecules participating in autoimmune responses, and raise the exciting possibility that the cells inducing autoimmune responses may finally be identified. Selective agents might then be developed which would interfere with or inhibit the cells. Understanding these developments requires detailed knowledge of how T cells recognize antigen, and of the receptors involved in autoimmune diseases. This article reviews the current literature on T cell receptor structure, and summarizes what is currently known about the usage of specific T cell receptors in autoimmune rheumatic disease.