A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes

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Abstract

We document here that infection of prediabetic mice with a virus expressing an H-2Kb–restricted mimic ligand to a self epitope present on β cells accelerates the development of autoimmune diabetes. Immunization with the mimic ligand expanded autoreactive T cell populations, which was followed by their trafficking to the islets, as visualized in situ by tetramer staining. In contrast, the mimic ligand did not generate sufficient autoreactive T cells in naive mice to initiate disease. Diabetes acceleration did not occur in H-2Kb–deficient mice or in mice tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens accelerate a previously established autoimmune process. Sequential heterologous viral infections might therefore act in concert to precipitate clinical autoimmune disease, even if single exposure to a viral mimic does not always cause sufficient tissue destruction.

Authors

Urs Christen, Kurt H. Edelmann, Dorian B. McGavern, Tom Wolfe, Bryan Coon, Meghann K. Teague, Stephen D. Miller, Michael B.A. Oldstone, Matthias G. von Herrath