title: Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection in mice.
abstract: Immune evasion by Lyme spirochetes is a multifactorial process involving numerous mechanisms. The OspE protein family undergoes antigenic variation during infection and binds factor H (fH) and possibly FHL-1/reconectin. In Borrelia burgdorferi B31MI, the OspE family consists of three paralogs: BBL39 (ErpA), BBP38, and BBN38 (ErpP). BBL39 and BBP38 are identical and therefore are referred to here as BBL39. The goals of this study were to assess the specificity of the antibody (Ab) response to the OspE paralogs and to identify the domains or determinants of OspE that are required for the binding of fH and OspE-targeting Abs that develop during infection. Here we demonstrate that at least some of the anti-OspE Abs produced during infection are paralog specific and that Ab binding requires conformational determinants whose formation requires both the N- and C-terminal domains of OspE. The binding of fH to OspE was also found to be dependent on conformational determinants. It is also demonstrated here that all of the OspE paralogs expressed by B. burgdorferi B31MI are capable of binding fH. The binding of fH to members of the OspF protein family was also assessed. In contrast to an earlier report, no binding of BBO39 or BBR42 to human fH was detected. Lastly, a series of competitive binding enzyme-linked immunosorbent assay analyses, designed to determine if fH and infection serum Abs bind to the same sites on OspE, revealed that these ligands interact with different regions of OspE.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond 23298-0678, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Metts
authors.forename: John V
authors.initials: JV
authors.lastname: McDowell
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
authors.forename: Paul Robert
authors.initials: PR
authors.lastname: Hansen
authors.forename: Richard Thomas
authors.initials: RT
authors.lastname: Marconi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D001667:Binding, Competitive; D017242:Complement Factor H / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C493495:CFH protein, human; D008074:Lipoproteins; C084998:OspE protein, Borrelia burgdorferi; D017242:Complement Factor H