Structural identification of a key protective B-cell epitope in Lyme disease antigen OspA

J Mol Biol. 2000 Oct 6;302(5):1153-64. doi: 10.1006/jmbi.2000.4119.


Outer surface protein A (OspA) is a major lipoprotein of the Borrelia burgdorferi spirochete, the causative agent of Lyme disease. Vaccination with OspA generates an immune response that can prevent bacterial transmission to a mammalian host during the attachment of an infected tick. However, the protective capacity of immune sera cannot be predicted by measuring total anti-OspA antibody. The murine monoclonal antibody LA-2 defines an important protective B-cell epitope of OspA against which protective sera have strong levels of reactivity. We have now mapped the LA-2 epitope of OspA using both NMR chemical-shift perturbation measurements in solution and X-ray crystal structure determination. LA-2 recognizes the three surface-exposed loops of the C-terminal domain of OspA that are on the tip of the elongated molecule most distant from the lipid-modified N terminus. The structure suggests that the natural variation at OspA sequence position 208 in the first loop is a major limiting factor for antibody cross-reactivity between different Lyme disease-causing Borrelia strains. The unusual Fab-dominated lattice of the crystal also permits a rare view of antigen flexibility within an antigen:antibody complex. These results provide a rationale for improvements in OspA-based vaccines and suggest possible designs for more direct tests of antibody protective levels in vaccinated individuals.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigen-Antibody Complex / chemistry
  • Antigen-Antibody Complex / immunology
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Antigens, Surface / chemistry*
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines
  • Borrelia burgdorferi Group / chemistry
  • Borrelia burgdorferi Group / genetics
  • Borrelia burgdorferi Group / immunology*
  • Crystallography, X-Ray
  • Epitope Mapping
  • Epitopes, B-Lymphocyte / chemistry*
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology*
  • Genetic Variation / genetics
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / immunology
  • Lipoproteins*
  • Lyme Disease / immunology*
  • Lyme Disease Vaccines / chemistry*
  • Lyme Disease Vaccines / genetics
  • Lyme Disease Vaccines / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment


  • Antigen-Antibody Complex
  • Antigens, Bacterial
  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Epitopes, B-Lymphocyte
  • Immunoglobulin Fab Fragments
  • Lipoproteins
  • Lyme Disease Vaccines
  • OspA protein

Associated data

  • PDB/1FJ1