ABSTRACT
I. OVERVIEW OF HUMAN AUTOIMMUNE DISEASE A. Disease Initiation There are two general hypotheses for the etiology of human autoimmune disorders. In the first instance, the organ becomes infected by a virus or other infectious agent and cells that infiltrate that organ are targeted to the infectious agent. These events would then begin the cascade leading to the organ-specific autoimmune disease. The alternative hypothesis is that the initial infiltrating cells are autoimmune and recognize the organ-specific proteins that are presented by local antigen-presenting cells in the context of MHC. At our present state of knowledge, either hypothesis is possible. However, once the autoimmune cascade begins it is likely that "epitope spreading" will occur, and T cells recognizing other organ-specific proteins will be recruited. Perhaps viruses and infectious agents acting as superantigens initially trigger or drive the autoimmune process, as opposed to being the primary target of infiltrating cells. Understanding the mechanism for initiation of autoimmune disorders and the range of antigens recognized by self-reactive T cells is critical for developing antigen-specific therapies for these disorders.
