An immunodominant conserved region within the variable domain of VlsE, thevariable surface antigen of Borrelia burgdorferi

Antigenic variation is an effective strategy evolved by pathogenic microbes to avoid immune destruction, Variable Ags such as the variable major prote in of Borrelia hermsii, the variant surface glycoprotein of African trypano somes, and the pilin of Neisseria gonorrhoeae include an immunodominant var iable domain and one or more invariable domains that are not antigenic. Sho rt, nonantigenic, invariable regions also may be present within the variabl e domain, VlsE (variable major protein-like sequence, expressed), the varia ble surface Ag of Borrelia burgdorferi, the Lyme disease spirochete, also c ontains both variable and invariable domains. In addition, interspersed wit hin the VlsE variable domain there are sis invariable regions (IR1-6) that together amount to half of this portion's primary structure, We show here t hat these IRs are conserved among strains and genospecies of the B. burgdor feri sensu late complex. Surprisingly, unlike the invariable regions of var iable major protein, variant surface glycoprotein, and pilin, which are not antigenic in natural infections, the most conserved of the IRs, IR6, is im munodominant in LS me disease patients and in monkeys infected with B, burg dorferi. IR6 is exposed on the surface of VlsE, as assessed by immunoprecip itation experiments, but is inaccessible to Ab on the spirochete's outer me mbrane, as demonstrated by immunofluorescence and in vitro killing assays, VlsE thus significantly departs from the antigenic variation paradigm, wher eby immunodominance is only manifest in variable portions, We submit that I R6 may act as a decoy epitope(s) and contribute to divert the,ib response f rost other, perhaps protective regions of VlsE.