SB2013 L04gr5: Difference between revisions
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Interspersed in the variable regions of the variable domain are six invariable regions (IR1-IR6). Although located on the membrane distal region of the protein, the IRs are buried within the protein and have little exposure to the surface. The IRs might be further hidden from surface exposure due to the possible dimerization of VlsE, forming a shield at the monomer-monomer interface.<ref name="Eicken" />These six IRs do not undergo changes during antigenic variation and are present in many strains and genospecies of ''B. burgdorferi''<ref name="Zhang and Norris" />. | Interspersed in the variable regions of the variable domain are six invariable regions (IR1-IR6). Although located on the membrane distal region of the protein, the IRs are buried within the protein and have little exposure to the surface. The IRs might be further hidden from surface exposure due to the possible dimerization of VlsE, forming a shield at the monomer-monomer interface.<ref name="Eicken" />These six IRs do not undergo changes during antigenic variation and are present in many strains and genospecies of ''B. burgdorferi''<ref name="Zhang and Norris" />. | ||
<scene name='SB2013_L04gr5/Ir6/1'>IR6</scene>, the second least exposed region composed of 26 amino acids (aa 274-298), has been found to be the most conserved IR and the most immunogenic as observed in studies involving mice, monkeys and humans. In a study conducted by Liang et al., serum samples from monkeys, patients and mice all infected with Lyme disease were collected and the immunogenicity of each invariable region was tested. In monkeys, the results showed a robust response to IR6 and little to no response to the remaining IRs. Similarly, only IR6 elicited a strong immune response in infected humans with the exception of one patient also having a response to IR4. The immunodomminance of IR6 is depicted in Figure 3. In mice, however, a strong response was detected across IRs 6, 2, and 4, but not in IRs 1, 3, and 5<ref name="Liang" />, thus demonstrating the immunodominance of IR6 across species and indicating that further research into the immunogenicity of IRs 2 and 4 is needed. Due to its highly conserved structure and immunodominance across species, IR6 can clearly be seen as an important factor to the functionality of ''B. burgdorferi'' and therefore benefits from its strategic placement indicated in the crystallized structure.<ref name="Eicken" /> | <scene name='SB2013_L04gr5/Ir6/1'>IR6</scene>, the second least exposed region composed of 26 amino acids (aa 274-298), has been found to be the most conserved IR and the most immunogenic<ref name="Liang" /> as observed in studies involving mice, monkeys and humans. In a study conducted by Liang et al., serum samples from monkeys, patients and mice all infected with Lyme disease were collected and the immunogenicity of each invariable region was tested. In monkeys, the results showed a robust response to IR6 and little to no response to the remaining IRs. Similarly, only IR6 elicited a strong immune response in infected humans with the exception of one patient also having a response to IR4. The immunodomminance of IR6 is depicted in Figure 3. In mice, however, a strong response was detected across IRs 6, 2, and 4, but not in IRs 1, 3, and 5<ref name="Liang" />, thus demonstrating the immunodominance of IR6 across species and indicating that further research into the immunogenicity of IRs 2 and 4 is needed. Due to its highly conserved structure and immunodominance across species, IR6 can clearly be seen as an important factor to the functionality of ''B. burgdorferi'' and therefore benefits from its strategic placement indicated in the crystallized structure.<ref name="Eicken" /> | ||
The high immunogenicity effect of IR6 is thought to only occur in dead bacteria due to its low maximal theoretical surface exposure in living ''B. borgderfuri'' (13.7%). Interaction with anti-IR6 antibodies would be limited to the exposed <scene name='SB2013_L04gr5/Ir6_residues/1'>amino acid residues</scene>, Lys-274, Gln-279, Lys-291, and Lys-294.<ref name="Eicken" /> These amino acids would be the likely targets of the host immune response. The immunodominant nature of VlsE, especially in IR6, makes it a viable diagnostic tool.<ref name="Marangoni" /> | The high immunogenicity effect of IR6 is thought to only occur in dead bacteria due to its low maximal theoretical surface exposure in living ''B. borgderfuri'' (13.7%). Interaction with anti-IR6 antibodies would be limited to the exposed <scene name='SB2013_L04gr5/Ir6_residues/1'>amino acid residues</scene>, Lys-274, Gln-279, Lys-291, and Lys-294.<ref name="Eicken" /> These amino acids would be the likely targets of the host immune response. The immunodominant nature of VlsE, especially in IR6, makes it a viable diagnostic tool.<ref name="Marangoni" /> | ||