Anti-Idiotype scFv Localizes an Autoepitope in the Globular Domain of C1q

• Main Authors: Nadezhda Todorova, Miroslav Rangelov, Vanya Bogoeva, Vishnya Stoyanova, Anna Yordanova, Ginka Nikolova, Hristo Georgiev, Daniela Dimitrova, Safa Mohedin, Katerina Stoyanova, Ivanka Tsacheva
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: C1q; globular autoepitopes; scFv; anti-DNA
• Online Access: https://www.mdpi.com/1422-0067/22/15/8288

We addressed the issue of C1q autoantigenicity by studying the structural features of the autoepitopes recognized by the polyclonal anti-C1q antibodies present in Lupus Nephritis (LN) sera. We used six fractions of anti-C1q as antigens and selected anti-idiotypic scFv antibodies from the phage library “Griffin.1”. The monoclonal scFv A1 was the most potent inhibitor of the recognition of C1q and its fragments ghA, ghB and ghC, comprising the globular domain gC1q, by the lupus autoantibodies. It was sequenced and in silico folded by molecular dynamics into a 3D structure. The generated 3D model of A1 elucidated CDR similarity to the apical region of gC1q, thus mapping indirectly for the first time a globular autoepitope of C1q. The V_H CDR2 of A1 mimicked the ghA sequence GSEAD suggested as a cross-epitope between anti-DNA and anti-C1q antibodies. Other potential inhibitors of the recognition of C1q by the LN autoantibodies among the selected recombinant antibodies were the monoclonal scFv F6, F9 and A12.