Cryptic and exposed invariable regions of VlsE, the variable surface antigen of Borrelia burgdorferi sl

Borrelia burgdorferi, the Lyme disease spirochete, possesses a surface prot ein,VlsE, which undergoes antigenic variation. VlsE contains two invariable domains and a variable one that includes six variable and six invariable r egions (IRs). Five of the IRs are conserved among strains and genospecies o f B. burgdorferi sensu late. IR, is conserved, immunodominant, and exposed at the VlsE surface but not at the spirochete surface, as assessed in vitro . In the present study, the remaining conserved IRs (IR2 to IR5) were inves tigated. Antisera to synthetic peptides based on each of the IR, to IR, seq uences were produced in rabbits. Antipeptide antibody titers were similarly high in all antisera. Native VlsE was immunoprecipitable with antibodies t o IR2, IR4, and IR5 but not to IR3, indicating that the first three sequenc es were exposed at the VlsE surface. However, negative surface immunofluore scence and in vitro antibody-mediated killing results indicated that none o f the IRs were accessible to antibody at the spirochetal surface in vitro.