Human autoimmune diseases are specific antigen-driven T-cell diseases: identification of the antigens.

We are investigating the hypothesis that most human autoimmune diseases are specific antigen-driven T-cell diseases. T-cell clones responding to specific antigenic epitopes are responsible for the initiation and/or the propagation of these diseases. Similarly, specific antigen-driven T-cell responses are responsible for the rejection of organ allografts and the immune response to tumors. Activated T cells provide the "engine" for the chronic inflammation that is associated with autoimmune diseases, organ graft rejection and tumor immunity. The best way to identify whether specific antigen-driven T cell responses are involved in the initiation and/or propagation of these disorders is to investigate whether T cells that infiltrate relevant tissues from these diseases contain monoclonal or oligoclonal, that is to say clonally expanded, populations of T cells. Identification of the T-cell antigen receptor (TCR) transcripts employed by the clonally expanded T cells in these patients permits the identification of the specific antigens that elicit these T-cell responses. These antigens may be responsible for the pathogenesis of these diseases. We will summarize here certain of our findings in this area of research.