User:Marvin O'Neal/VlsE: Difference between revisions
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VlsE is a surface lipoprotein of Borrelia burdorferi, the causative agent of Lyme Disease. It undergoes antigenic variation that seems important to evasion of the host’s immune system. In addition, the protein is used for Lyme Disease diagnosis. It is composed of four similar subunits each possessing two invariable domains and one variable domain (1, 2). This model represents just one of these subunits with focus on the variable domain. It contains six variable regions (VRs), highlighted in green, and six invariable regions (IR1-IR6). The invariable regions are largely embedded in the protein and remain relatively unchanged within the host and across strains. IR6, a 26 amino acid long region highlighted in red and yellow, exhibits immunodominance (5, 6). The variable regions encompass 37% of the VlsE’s exposed surface area despite comprising only 25% of the protein (1, 2). However, 50% percent of the VR surface area is exposed while IR6, in contrast, exposes just 13.7% of its surface area. This leaves only four amino residues of the antigenic IR6 unprotected; lysine-276, glutamine-279, lysine-291, and lysine-294, colored yellow. Thus it is almost entirely embedded in the protein, highlighted red, and shielded by the variable regions (2). | VlsE is a surface lipoprotein of Borrelia burdorferi, the causative agent of Lyme Disease. <br> It undergoes antigenic variation that seems important to evasion of the host’s immune system. In addition, the protein is used for Lyme Disease diagnosis. It is composed of four similar subunits each possessing two invariable domains and one variable domain (1, 2). This model represents just one of these subunits with focus on the variable domain. It contains six variable regions (VRs), highlighted in green, and six invariable regions (IR1-IR6). The invariable regions are largely embedded in the protein and remain relatively unchanged within the host and across strains. IR6, a 26 amino acid long region highlighted in red and yellow, exhibits immunodominance (5, 6). The variable regions encompass 37% of the VlsE’s exposed surface area despite comprising only 25% of the protein (1, 2). However, 50% percent of the VR surface area is exposed while IR6, in contrast, exposes just 13.7% of its surface area. This leaves only four amino residues of the antigenic IR6 unprotected; lysine-276, glutamine-279, lysine-291, and lysine-294, colored yellow. Thus it is almost entirely embedded in the protein, highlighted red, and shielded by the variable regions (2). | ||
The variable region rapidly undergoes the recombination event leading to variation with an estimated 1030 possible combinations, far exceeding the number of antibodies found in the human immune system (6). This rapid recombination is initiated by the host’s cytokines, while absence of those cytokines results in a decreased bacterial burden (3). It is speculated that absence of cytokines leads to little VR variation and proffer cytokine inhibition as a potential avenue of investigation for alternative vaccination (7). The nature of variable regions makes it unlikely that enough of one VR variation will be present in large enough supply to create an immunodominant variable region (6). Thus cytokine inhibition would enable elicitation of an antibody response by the VR regions, which are exposed to antibody binding, negating its shielding effect on IR6. As mentioned, shielding of the immunodominant IR6 by regions which constantly vary allows for IR6 to elicit an immune response while remaining inaccessible to antibody binding. This combined with the decreased bacterial burden observed in absence of cytokines, and presumably little VR variation, supports the speculated importance of VlsE in evasion of the immune system (2, 3, 5). | The variable region rapidly undergoes the recombination event leading to variation with an estimated 1030 possible combinations, far exceeding the number of antibodies found in the human immune system (6). This rapid recombination is initiated by the host’s cytokines, while absence of those cytokines results in a decreased bacterial burden (3). It is speculated that absence of cytokines leads to little VR variation and proffer cytokine inhibition as a potential avenue of investigation for alternative vaccination (7). The nature of variable regions makes it unlikely that enough of one VR variation will be present in large enough supply to create an immunodominant variable region (6). Thus cytokine inhibition would enable elicitation of an antibody response by the VR regions, which are exposed to antibody binding, negating its shielding effect on IR6. As mentioned, shielding of the immunodominant IR6 by regions which constantly vary allows for IR6 to elicit an immune response while remaining inaccessible to antibody binding. This combined with the decreased bacterial burden observed in absence of cytokines, and presumably little VR variation, supports the speculated importance of VlsE in evasion of the immune system (2, 3, 5). | ||
