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Infection and Immunity, September 1998, p. 4073-4079, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Dominant Epitope of Borrelia garinii Outer Surface Protein C Recognized by Sera from Patients with Neuroborreliosis Has a Surface-Exposed Conserved Structural Motif

Marianne J. Mathiesen,1 Arne Holm,2 Michael Christiansen,1 Jens Blom,3 Klaus Hansen,1 Søren Østergaard,2,dagger and Michael Theisen1,*

Department of Clinical Biochemistry1 and Department of Molecular Cell Biology,3 Statens Serum Institut, and Department of Chemistry, Royal Veterinary and Agricultural University,2 Copenhagen, Denmark

Received 4 March 1998/Returned for modification 8 April 1998/Accepted 27 May 1998

Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis.

* Corresponding author. Mailing address: Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Phone: (45) 32683779. Fax: (45) 32683228. E-mail: mth{at}ssi.dk.

dagger Present address: Novo Research Institute, Bagsværd, Denmark.

Infection and Immunity, September 1998, p. 4073-4079, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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