Purchase this article with an account.
CA Deeg, SR Thurau, H Gerhards, B Kaspers, G Wildner; Epitope Spreading in Induced and Spontaneous Equine Recurrent Uveitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1532.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Immunization with a multideterminant native antigen leads to induction of the T cell response to one or more of its dominant determinants. There is no reaction to other regions of the same antigen, therefore these determinants are cryptic epitopes. T cells specific for these cryptic endogenous epitopes activated during acute inflammation could play the major effector role in subsequent relapses of autoimmune uveitis, as it was demonstrated for other autoimmune diseases as EAE or autoimmune diabetes. The goal of our study was the investigation of the T cell response of horses with IRBP induced uveitis (HEU) to various S-Antigen and IRBP derived peptides at several timepoints during the uveitic attack and subsequent induced relapses. Methods: We induced uveitis in horses by two s.c. injections of IRBP emulsified in CFA. Relapses were induced by two subsequent immunizations at day 56 and 84. Control horses received CFA only. In vitro proliferation of PBL was analyzed at day 0, 2, 4, 6, 8 and 12 after each immunization of experimental and control horses. Results: All horses developed uveitis at day 6-7 after the second immunization. Intramolecular epitope spreading to other IRBP epitopes was recognized after the second immunization in all horses of the experimental group. Novel reactivity was observed after every subsequent immunization, combined with a loss of reactivity to some of the peptides that were recognized at the beginning. More interestingly, we also found intermolecular epitope spreading to S-Ag in 5 out of 7 horses after the second immunization. At that timepoint peripheral blood derived lymphocytes proliferated in response to S-Ag derived peptides such as PD-SAg, peptide M and SAg 281. We could also observe intramolecular and intermolecular epitope spreading in horses with spontaneous equine recurrent uveitis. Conclusion: These findings underscore the possibility that the progression of autoimmune uveitis could be perpetuated by a shifting of T cell autoreactivity from a single predominant determinant to other uveitogenic epitopes.
This PDF is available to Subscribers Only