SB2013 L04gr5: Difference between revisions

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The variable regions’ location also supports the potential role that the protein plays in evading host immune responses through [http://en.wikipedia.org/wiki/Gene_conversion gene conversion] (Zhang and Norris 1998). These regions are hypothesized to expose highly variable [http://en.wikipedia.org/wiki/Epitopes epitopes], which would prevent the immune system from recognizing the antigen and subsequently prevent the onset of Lyme disease (Eicken 2002). This feature starkly contrasts to the invariable regions, which does not undergo constant variation and whose genetic composition remains mostly conserved (Zhang and Norris 1998).

=Invariable Regions=

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. IRs might be further hidden from surface exposure due to the possible dimerization of VlsE, forming a shield at the monomer-monomer interface (Eicken et al 2002). These six IRs do not undergo changes during antigenic variation and are present in many strains and genospecies of B. burgdorferi. IR6, the second least exposed region composed of 26 amino acids, has been found to be the most conserved IR and the most immunogenic as observed in studies involving monkeys and humans. In a study conducted by Liang et al., serum samples from 10 rhesus monkeys were infected by the bite of Ixodes scapularis nymphal ticks. The antibody response was measured 4-6 weeks later by peptide-based ELISA. The results showed a robust response to IR6 and little to no response to the remaining IRs. To investigate the antigenicity of IRs in humans, 15 samples were collected from Lyme disease patients. As seen with monkeys, only IR6 elicited a strong immune response.(Figure with graphs). However, when a similar infection was induced in mice, a strong response was detected across IR6, IR2, and IR4. (Liang et al 1999 A), thus demonstrating the importance of IR6 across many species and indicating that further research into the IRs 2 and 4 is needed.Clearly, due to its highly conserved structure and immunodominance, IR6 is important to the functionality of B. Burgdorferi and therefore requires its strategic placement indicated in the crystallized structure (Eicken et al 2002).

The high immunogenicity effect of IR6 is thought to only occur in dead bacteria due to its low exposure in living B. borgderfuri. Interaction with anti-IR6 antibodies would be limited to the exposed amino acid residues, Lys-274, Gln-, Lys-,Lys-. These amino acids would be the likely targets of the host immune response. The immunodominant nature of VlsE, especially in IR6, makes it viable diagnostic tool.

SB2013 L04gr5: Difference between revisions

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 The variable regions’ location also supports the potential role that the protein plays in evading host immune responses through [http://en.wikipedia.org/wiki/Gene_conversion gene conversion] (Zhang and Norris 1998). These regions are hypothesized to expose highly variable [http://en.wikipedia.org/wiki/Epitopes epitopes], which would prevent the immune system from recognizing the antigen and subsequently prevent the onset of Lyme disease (Eicken 2002). This feature starkly contrasts to the invariable regions, which does not undergo constant variation and whose genetic composition remains mostly conserved (Zhang and Norris 1998).
+=Invariable Regions=
+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.  IRs might be further hidden from surface exposure due to the possible dimerization of VlsE, forming a shield at the monomer-monomer interface (Eicken et al 2002). These six IRs do not undergo changes during antigenic variation and are present in many strains and genospecies of B. burgdorferi. IR6, the second least exposed region composed of 26 amino acids, has been found to be the most conserved IR and the most immunogenic as observed in studies involving monkeys and humans.  In a study conducted by Liang et al., serum samples from 10 rhesus monkeys were infected by the bite of Ixodes scapularis nymphal ticks. The antibody response was measured 4-6 weeks later by peptide-based ELISA. The results showed a robust response to IR6 and little to no response to the remaining IRs.  To investigate the antigenicity of IRs in humans, 15 samples were collected from Lyme disease patients. As seen with monkeys, only IR6 elicited a strong immune response.(Figure with graphs).  However, when a similar infection was induced in mice, a strong response was detected across IR6, IR2, and IR4. (Liang et al 1999 A), thus demonstrating the importance of IR6 across many species and indicating that further research into the IRs 2 and 4 is needed.Clearly, due to its highly conserved structure and immunodominance, IR6 is important to the functionality of B. Burgdorferi and therefore requires its strategic placement indicated in the crystallized structure (Eicken et al 2002).
+The high immunogenicity effect of IR6 is thought to only occur in dead bacteria due to its low exposure in living B. borgderfuri. Interaction with anti-IR6 antibodies would be limited to the exposed amino acid residues, Lys-274, Gln-, Lys-,Lys-. These amino acids would be the likely targets of the host immune response.  The immunodominant nature of VlsE, especially in IR6, makes it viable diagnostic tool.