How human IgGs against myelin basic protein (MBP) recognize oligopeptides and MBP

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Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis. It was shown that the minimal ligands of the light chains of IgGs are many different free AAs (Kd = 0.51–0.016 M), and each free AA interacts with the specific subsite of the light chain intended for recognition of this AA in specific LSRFSW oligopeptide. A gradual transition from Leu to LSRFSWGAEGQK leads to an increase in the affinity from 10−1 to 2.3 × 10−4 M because of additive interactions of the light chain with 6 AAs of this oligopeptide and then the affinity reaches plateau. The contributions of 6 various AAs to the affinity of the oligopeptide are different (Kd, M): 0.71 (S), 0.44 (R), 0.14 (F), 0.17 (S), and 0.62 (W). Affinity of nonspecific oligopeptides to the light chains of IgGs is significantly lower. Intact MBP interacts with both light and heavy chains of IgGs demonstrating 192-fold higher affinity than the specific oligopeptide. It is a first quantitative analysis of the mechanism of proteins recognition by antibodies. The thermodynamic model was constructed to describe the interactions of IgGs with MBP. The data obtained can be very useful for understanding how antibodies against many different proteins can recognize these proteins.

Original languageEnglish
Article number2637
Number of pages12
JournalJournal of Molecular Recognition
Issue number10
Publication statusPublished - 1 Oct 2017


  • general regularities of protein recognition
  • human anti-MBP antibodies
  • myelin basic protein (MBP)
  • recognition of peptides and MBP
  • thermodynamic model of recognition
  • DNA
  • Humans
  • Middle Aged
  • Oligopeptides/chemistry
  • Chromatography, Thin Layer
  • Thermodynamics
  • Adult
  • Cross-Linking Reagents/metabolism
  • Immunoglobulin G/metabolism
  • Amino Acid Sequence
  • Immunoglobulin Light Chains/metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Myelin Basic Protein/immunology
  • Ligands
  • Kinetics


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