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

• Published in: Immune network Vol. 21; no. 5; pp. 34 - 49
• Main Authors: Lee, Ahreum, Yoo, Duck Kyun, Lee, Yonghee, Jeon, Sumin, Jung, Suhan, Noh, Jinsung, Ju, Soyeon, Hwang, Siwon, Kim, Hong Hee, Kwon, Sunghoon, Chung, Junho, Choi, Youngnim
• Format: Journal Article
• Language: English
• Published: 대한면역학회 01.10.2021; The Korean Association of Immunologists
• Subjects: Original; 면역학; Molecular mimicry; Mice; Autoantibodies; Aquaporin-5; Sjogren"s syndrome
• ISSN: 1598-2629; 2092-6685
• DOI: 10.4110/in.2021.21.e34

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 AQP5E-specific 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.