Aire-mediated central tolerance includes na�ve but not post-translational modified self-antigens

Event Abstract Back to Event Aire-mediated central tolerance includes naïve but not post-translational modified self-antigens Bruno Raposo1, Patrick Merky1, Rikard Holmdahl1 and Johan Bäcklund1* 1 Karolinska Institutet, Medical Biochemistry and Biophysics, Sweden The autoimmune regulator (Aire) controls ectopic expression of peripheral tissue-restricted antigens (TRAs) in medullary thymic epithelial cells, and is involved in mediating deletion of autoreactive T cells in the thymus. Despite the relevant role of Aire in regulating tolerance to TRAs, autoreactive T cells are frequently observed within the mature T cell repertoire. Many self-antigens are naturally subjected to post-translational modifications, such as glycosylation, and it is possible that such modified TRAs are not sufficiently presented to induce tolerance in the thymus. Here we have investigated the regulation of tolerance to type II collagen (CII), a self-antigen naturally subjected to glycosylation. Using an autologous collagen-induced arthritis model, where the transgenic expression of CII is Aire-dependent, we show that tolerance to CII is restricted to the non-modified version of the autoantigen, whereas T cells specific for the glycosylated version escape central tolerance. This finding explains earlier observations that the glycosylated form of CII constitutes the immunodominant epitope, despite that peripherally expressed self-CII appears uniformly glycoslylated. However, as many self-antigens are naturally subjected to posttranslational modifications or may become altered over time either spontaneously or due to traumas, our data points out a possible general mechanism whereby T cells may escape an otherwise efficient tolerogenic mechanism. Keywords: posttranslational modifications, AIRE, collagen-induced arthritis, Central Tolerance, Glycosylation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Raposo B, Merky P, Holmdahl R and Bäcklund J (2013). Aire-mediated central tolerance includes naïve but not post-translational modified self-antigens. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00295 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Johan Bäcklund, Karolinska Institutet, Medical Biochemistry and Biophysics, Stockholm, 171 77, Sweden, Johan.Backlund@ki.se Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bruno Raposo Patrick Merky Rikard Holmdahl Johan Bäcklund Google Bruno Raposo Patrick Merky Rikard Holmdahl Johan Bäcklund Google Scholar Bruno Raposo Patrick Merky Rikard Holmdahl Johan Bäcklund PubMed Bruno Raposo Patrick Merky Rikard Holmdahl Johan Bäcklund Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.