Immune Netw.
2021 Oct;21(5):e34. 10.4110/in.2021.21.e34.
Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
- Affiliations
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- 1Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea
- 2Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea
- 3Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Korea
- 4Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Korea
- 5Department of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 08826, Korea
- 6Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Korea
- 7BK21+ Creative Research Engineer Development for IT, Seoul National University, Seoul 08826, Korea
- 8Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea
- 9Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul 08826, Korea
- 10Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea
- KMID: 2522152
- DOI: http://doi.org/10.4110/in.2021.21.e34
Abstract
- Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell “E” epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the “E” epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5Especific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.
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