Independent Antibody Interaction and Co-Operative Antibody Interaction Models.
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Abstract
<p><b><i>Independent Antibody Interaction Model</i></b> (Panel <b>A</b>): If the ligand-receptor interactions are independent of each other, invasion by either EBA-175 (Route 1) or by RH5 (Route 2) is not affected by the other. Thus, in the presence of both anti-EBA-175<sub>RII</sub> and anti-rRH5 antibodies, the expected inhibition from the combination anti-sera is ADDITIVE (synergistic) when compared to the inhibition from the individual anti-sera. <b><i>Co-Operative Antibody Interaction Model</i></b> (Panel <b>B</b>): If the ligand-receptors act in a co-operative method, then invasion by EBA-175 (Route 1) and RH5 (Route 2) are not independent of each other. Thus, in the presence of anti-EBA-175<sub>RII</sub> and anti-rRH5 antibodies, the expected inhibition from the combination anti-sera is only as effective as the most active individual antibody. <b><i>Antibody Steric Hindrance</i></b> (Panels <b>C</b> and <b>D</b>): Data suggests that EBA-175 abundance is greater than RH5 and is possibly released before RH5 (Ord et al, unpublished observations). At LOW antibody concentrations (<b>C</b>), there is no possible hindrance of RH5 by EBA-175, and all available antibodies are able to bind to their respective ligands independently. This is observed as growth inhibition with the combination anti-sera being more effective than that observed with the individual antibodies, i.e., it follows the Independent Antibody Interaction Model (<b>A</b>). Conversely, at HIGH antibody concentrations (<b>D</b>), anti-EBA-175 antibodies are able to bind to available EBA-175 ligands but they sterically hinder some RH5 antibody/ligand interactions, leaving some RH5 ligands available for invasion through the RH5 ligand/receptor pathways. This is observed as growth inhibition with the combination anti-sera being only as effective as anti-EBA-175<sub>RII</sub> sera alone, i.e. it follows the Co-Operative Antibody Interaction Model (<b>B</b>).</p