title: Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross-react with myelin basic protein and EBV antigen.
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 patients 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.
authors.affiliation: M. M. Shemyakin and Y. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia. gabibov@mx.ibch.ru
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Gabibov
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Belogurov
authors.forename: Yakov A
authors.initials: YA
authors.lastname: Lomakin
authors.forename: Maria Yu
authors.initials: MY
authors.lastname: Zakharova
authors.forename: Marat E
authors.initials: ME
authors.lastname: Avakyan
authors.forename: Viktorya V
authors.initials: VV
authors.lastname: Dubrovskaya
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Smirnov
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Ivanov
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Molnar
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Gurtsevitch
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Diduk
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Smirnova
authors.forename: Bérangère
authors.initials: B
authors.lastname: Avalle
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Sharanova
authors.forename: Alfonso
authors.initials: A
authors.lastname: Tramontano
authors.forename: Alain
authors.initials: A
authors.lastname: Friboulet
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Boyko
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ponomarenko
authors.forename: Nina V
authors.initials: NV
authors.lastname: Tikunova
mesh_terms: D000328:Adult; D000368:Aged; D000916:Antibody Diversity; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D018716:Molecular Mimicry; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000209:etiology / Q000276:immunology* / Q000821:virology*; D004676:Myelin Basic Protein / Q000276:immunology*; D019151:Peptide Library; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology; D040681:Structural Homology, Protein; D014763:Viral Matrix Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D001323:Autoantibodies; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C499048:MBP protein, human; D004676:Myelin Basic Protein; D019151:Peptide Library; D057127:Single-Chain Antibodies; D014763:Viral Matrix Proteins