Heavy-light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation

Yakov A. Lomakin, Maria Yu Zakharova, Alexey V. Stepanov, Maria A. Dronina, Ivan V. Smirnov, Tatyana V. Bobik, Andrey Yu Pyrkov, Nina V. Tikunova, Svetlana N. Sharanova, Vitali M. Boitsov, Sergey Yu Vyazmin, Marsel R. Kabilov, Alexey E. Tupikin, Alexey N. Krasnov, Nadezda A. Bykova, Yulia A. Medvedeva, Marina V. Fridman, Alexander V. Favorov, Natalia A. Ponomarenko, Michael V. DubinaAlexey N. Boyko, Valentin V. Vlassov, Alexey A. Belogurov, Alexander G. Gabibov

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development of such pathologies and, in particular, production of autoantibodies of different specificities. The combination of deep-sequencing technology with functional studies of antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features in the repertoires of autoreactive B cells. Here, we have analyzed cross-combinations of the variable regions of human immunoglobulins against the myelin basic protein (MBP) previously selected from a multiple sclerosis (MS)-related scFv phage-display library. On the other hand, we have performed deep sequencing of the sublibraries of scFvs against MBP, Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), and myelin oligodendrocyte glycoprotein (MOG). Bioinformatics analysis of sequencing data and surface plasmon resonance (SPR) studies have shown that it is the variable fragments of antibody heavy chains that mainly determine both the affinity of antibodies to the parent autoantigen and their cross-reactivity. It is suggested that LMP1-cross-reactive anti-myelin autoantibodies contain heavy chains encoded by certain germline gene segments, which may be a hallmark of the EBV-specific B cell subpopulation involved in MS triggering.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalMolecular Immunology
Issue number2
StatePublished - Dec 1 2014


  • Antibody cross-reactivity
  • B cells deep sequencing
  • Epstein-Barr virus
  • Human germline autoantibody gene segments
  • Latent membrane protein 1
  • Multiple sclerosis
  • Myelin basic protein

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology


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