Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross-react with myelin basic protein and EBV antigen

Alexander G. Gabibov, Alexey A. Belogurov, Yakov A. Lomakin, Maria Yu Zakharova, Marat E. Avakyan, Viktorya V. Dubrovskaya, Ivan V. Smirnov, Alexis S. Ivanov, Andrey A. Molnar, Vladimir E. Gurtsevitch, Sergey V. Diduk, Ksenia V. Smirnova, Bérangère Avalle, Svetlana N. Sharanova, Alfonso Tramontano, Alain Friboulet, Alexey N. Boyko, Natalia A. Ponomarenko, Nina V. Tikunova

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with unknown etiology. It is increasingly evident that, together with pathogenic T cells, autoreactive B cells are among the major players in MS development. The analysis of myelin neuroantigen-specific antibody repertoires and their possible cross-reactivity against environmental antigens, including viral proteins, could shed light on the mechanism of MS induction and progression. A phage display library of single-chain variable fragments (scFvs) was constructed from blood lymphocytes of patienst with MS as a potential source of representative MS autoantibodies. Structural alignment of 13 clones selected toward myelin basic protein (MBP), one of the major myelin antigens, showed high homology within variable regions with cerebrospinal fluid MS-associated antibodies as well as with antibodies toward Epstein-Barr latent membrane protein 1 (LMP1). Three scFv clones showed pronounced specificity to MBP fragments 65-92 and 130-156, similar to the serum MS antibodies. One of these clones, designated E2, in both scFv and full-size human antibody constructs, was shown to react with both MBP and LMP1 proteins in vitro, suggesting natural cross-reactivity. Thus, antibodies induced against LMP1 during Epstein-Barr virus infection might act as inflammatory trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS pathogenesis.

Original languageEnglish (US)
Pages (from-to)4211-4221
Number of pages11
JournalFASEB Journal
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2011

Keywords

  • Epstein-Barr virus
  • Latent membrane protein 1
  • Phage-display library

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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