VlsE Control Protein

Background

Variable Lipoprotein Surface-Exposed protein, or VlsE, is a lipoprotein on the surface of the Lyme Disease spirochete Borrelia burgdorferi, detectable during all its life stages. It can exist as many different isoforms. VlsE has variable regions (VRs) and invariable regions (IRs). Some IRs are anchored in the outer membrane of the bacteria and some are antigens exposed on the membrane surface. Replacement of the VR by Borrelia within days of being transferred to a mammalian host presents new surface antigens to the host immune system, and helps Borrelia avoid a strong reaction by host immune systems. The VlsE is apparently not modified as much in the tick or in the rodent vector, when compared to in the mammal host. Several putative envelope proteins of B. burgdorferi appear to be expressed only in the infected mammalian host. The VRs are antigenic, irregularly shaped loops on the bacterial surface which may help to hide both membrane-incorporated and surface portions of adjacent proteins from immune cells. These VR loops are coded by antigenic cassettes. The protein loops can therefore be switched in or out of the protein, or different type loops traded. In B. burgdorferi there seem to be at least fifteen different VlsE cassettes that can insert into any of the variable regions of VlsE, allowing it to appear as millions of different antigens. Similar, but smaller, systems also operate for OSP-A, OSP-B, OSP-C, and other proteins. Some current research involves determination of control of cassette activation. One IR region, C6, of the VlsE protein, consistently stimulates a strong immune response. Its presentation may be a decoy that misdirects the immune system from less protected sites by causing competition for binding antibodies. The bound antibodies are thus not available for binding important therapeutic proteins. This may help Borrelia to enter T-cells, leading to their destruction. Because IR6 is invariable and found in all life stages of B. burgdorferi, it has been used in an ELISA diagnostic test for early IgM of Lyme Disease. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.