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

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

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

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Molecular mimicry can accelerate but not easily initiate autoimmune diab...
Molecular mimicry can accelerate but not easily initiate autoimmune diabetes. (A) Molecular mimicry is insufficient to prime naive autoreactive CD8 T cells and cause autoimmune diabetes. RIP-LCMV-NP mice were infected with 105 PFU LCMV-Arm (open circles), LCMV-Arm-Var (filled triangles), or PV alone (filled circles). (B) Primed autoreactive cells can become activated via molecular mimicry and accelerate disease. RIP-LCMV-NP mice were infected with either 105 PFU LCMV-Arm (open circles, filled circles) or 105 PFU PV (open triangles, filled triangles) on day 0 and, as indicated, received a secondary inoculation (2nd inf.) with PV (open triangles, filled circles) 28 days after the priming LCMV infection. As a comparison, the incidence data to RIP-LCMV-NP mice infected with LCMV alone are displayed (open circles). For both studies, blood glucose values were determined at weekly intervals. Mice with blood glucose levels above 300 mg/dl were considered diabetic. It is evident from these studies that secondary infection but not primary infection with PV can accelerate T1D development. Statistical analysis was done using the log rank test. Note that the diabetes onset curves for the groups LCMV alone versus LCMV-PV are significantly different (P = 0.0066).