Liang F T, Alvarez A L, Gu Y, Nowling J M, Ramamoorthy R, Philipp M T
Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, LA 70433, USA.
J Immunol. 1999 Nov 15;163(10):5566-73.
Antigenic variation is an effective strategy evolved by pathogenic microbes to avoid immune destruction. Variable Ags such as the variable major protein of Borrelia hermsii, the variant surface glycoprotein of African trypanosomes, and the pilin of Neisseria gonorrhoeae include an immunodominant variable domain and one or more invariable domains that are not antigenic. Short, nonantigenic, invariable regions also may be present within the variable domain. VlsE (variable major protein-like sequence, expressed), the variable surface Ag of Borrelia burgdorferi, the Lyme disease spirochete, also contains both variable and invariable domains. In addition, interspersed within the VlsE variable domain there are six invariable regions (IR1-6) that together amount to half of this portion's primary structure. We show here that these IRs are conserved among strains and genospecies of the B. burgdorferi sensu lato complex. Surprisingly, unlike the invariable regions of variable major protein, variant surface glycoprotein, and pilin, which are not antigenic in natural infections, the most conserved of the IRs, IR6, is immunodominant in Lyme disease patients and in monkeys infected with B. burgdorferi. IR6 is exposed on the surface of VlsE, as assessed by immunoprecipitation experiments, but is inaccessible to Ab on the spirochete's outer membrane, as demonstrated by immunofluorescence and in vitro killing assays. VlsE thus significantly departs from the antigenic variation paradigm, whereby immunodominance is only manifest in variable portions. We submit that IR6 may act as a decoy epitope(s) and contribute to divert the Ab response from other, perhaps protective regions of VlsE.
抗原变异是致病微生物进化出的一种有效策略，用于避免免疫破坏。可变抗原，如赫氏疏螺旋体的可变主要蛋白、非洲锥虫的可变表面糖蛋白和淋病奈瑟菌的菌毛蛋白，都包含一个免疫显性可变结构域和一个或多个无抗原性的恒定结构域。可变结构域内也可能存在短的、无抗原性的恒定区域。莱姆病螺旋体——伯氏疏螺旋体的可变表面抗原VlsE（表达的可变主要蛋白样序列）也同时包含可变和恒定结构域。此外，在VlsE可变结构域中散布着六个恒定区域（IR1 - 6），它们共同构成了该部分一级结构的一半。我们在此表明，这些恒定区域在广义伯氏疏螺旋体复合体的菌株和基因种之间是保守的。令人惊讶的是，与可变主要蛋白、可变表面糖蛋白和菌毛蛋白的恒定区域不同，这些恒定区域在自然感染中无抗原性，而最保守的恒定区域IR6在莱姆病患者和感染伯氏疏螺旋体的猴子中具有免疫显性。通过免疫沉淀实验评估，IR6暴露于VlsE表面，但免疫荧光和体外杀伤试验表明，它在螺旋体外膜上无法被抗体识别。因此，VlsE显著偏离了抗原变异模式，在该模式中免疫显性仅在可变部分表现出来。我们认为IR6可能作为一个诱饵表位，有助于将抗体反应从VlsE的其他可能具有保护作用的区域转移开。
