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.
Garza
K M
KM
Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
Lou
Y H
YH
Tung
K S
KS
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000209:etiology*; D004527:Egg Proteins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D009869:Oophoritis / Q000209:etiology; D010053:Ovary / Q000276:immunology*; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000502:physiology*; D000072216:Zona Pellucida Glycoproteins
D001323:Autoantibodies; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins