Role of Helical Structure in MBP Immunodominant Peptides for Efficient IgM Antibody Recognition in Multiple Sclerosis

Agnieszka Staśkiewicz; Michael Quagliata; Feliciana Real-Fernandez; Francesca Nuti; Roberta Lanzillo; Vincenzo Brescia-Morra; Hendrik Rusche; Michal Jewginski; Alfonso Carotenuto; Diego Brancaccio; Rina Aharoni; Ruth Arnon; Paolo Rovero; Rafal Latajka; Anna Maria Papini

doi:10.3389/fchem.2022.885180

Role of Helical Structure in MBP Immunodominant Peptides for Efficient IgM Antibody Recognition in Multiple Sclerosis

Front Chem. 2022 Jun 20:10:885180. doi: 10.3389/fchem.2022.885180. eCollection 2022.

Authors

Agnieszka Staśkiewicz^{1

2}, Michael Quagliata¹, Feliciana Real-Fernandez¹, Francesca Nuti¹, Roberta Lanzillo³, Vincenzo Brescia-Morra³, Hendrik Rusche^{4

5}, Michal Jewginski², Alfonso Carotenuto⁶, Diego Brancaccio⁶, Rina Aharoni⁷, Ruth Arnon⁷, Paolo Rovero⁸, Rafal Latajka², Anna Maria Papini^{1

5}

Affiliations

¹ Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy.
² Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland.
³ Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.
⁴ Fischer Analytics GmbH, Weiler, Germany.
⁵ CY PeptLab Platform of Peptide and Protein Chemistry and Biology and UMR 8076 CNRS-BioCIS, CNRS, CY Cergy Paris Université, Neuville sur Oise, France.
⁶ Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
⁷ Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
⁸ Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, University of Florence, Sesto Fiorentino, Italy.

Abstract

The involvement of Myelin Basic Protein (MBP) in Multiple Sclerosis (MS) has been widely discussed in the literature. This intrinsically disordered protein has an interesting α-helix motif, which can be considered as a conformational epitope. In this work we investigate the importance of the helical structure in antibody recognition by MBP peptides of different lengths. Firstly, we synthesized the peptide MBP (81-106) (1) and observed that its elongation at both N- and C-termini, to obtain the peptide MBP (76-116) (2) improves IgM antibody recognition in SP-ELISA, but destabilizes the helical structure. Conversely, in competitive ELISA, MBP (81-106) (1) is recognized more efficiently by IgM antibodies than MBP (76-116) (2), possibly thanks to its more stable helical structure observed in CD and NMR conformational experiments. These results are discussed in terms of different performances of peptide antigens in the two ELISA formats tested.

Keywords: NMR; circular dichroism; immune response; multiple sclerosis; myelin basic protein antigen; peptide-antigen based ELISA; synthetic helical peptides.