The dominant epitope of Borrelia garinii outer surface protein C recognized by sera from patients with neuroborreliosis has a surface-exposed conserved structural motif.
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.
Mathiesen
M J
MJ
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
Holm
A
A
Christiansen
M
M
Blom
J
J
Hansen
K
K
Ostergaard
S
S
Theisen
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D001667:Binding, Competitive; D001898:Borrelia / Q000276:immunology*; D001899:Borrelia Infections / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D007075:Immunoglobulin M; C079616:OspC protein