Mechanism of ovarian autoimmunity: induction of T cell and antibody responses by T cell epitope mimicry and epitope spreading.

Autoimmune diseases are often manifested as organ inflammation with loss of function, and detectable autoreactive T cell and autoantibody responses. In the proper genetic context, we have shown that these parameters of autoimmunity can result from a single pivotal event: the induction of a strong and persistent T cell response for a foreign or unrelated self peptide that mimics the target self peptide. This may apply to organ-specific and systemic autoimmunity, independent of whether the tissue inflammation results from T cell immune mechanism or antibodies. T cell peptide mimicry, through sharing of critical residues or by a less defined mechanism, can result in autoimmune disease. Once triggered, the helper T cell response leads rapidly to a concomitant autoantibody response spreading to distant B cell determinants of the self protein antigen. Evidently, with T cell help, endogenous antigens can stimulate B cells to provoke a functional autoantibody response against conformational antigenic determinants. These findings are based on recent studies on a novel autoimmune ovarian disease model induced by a self peptide with well-defined T and B cell epitopes. However, studies reported on systemic lupus erythematosus models have shown that similar events may result in autoantibody response in systemic autoimmunity.