Analysis of idiotope variability as a function of distance from the binding site for anti-streptococcal group A carbohydrate antibodies.
We have extended our analysis of rat monoclonal anti-idiotopes (anti-Id) specific for previously mapped binding site-associated (distal) and less-or nonbinding site-associated (proximal) idiotopes on a murine monoclonal anti-streptococcal group A carbohydrate (GAC) antibody. By utilizing other monoclonal anti-GAC antibodies and anti-idiotypic antibodies as radiolabeled probands in both competitive and direct radioimmunoassays, we have detected previously unsuspected reactivities of some of the anti-Id. Although the anti-Id recognizing the most proximal idiotopes manifest relatively narrow ranges of binding strengths for anti-GAC antibodies, the anti-Id recognizing the most distal idiotopes display broader, more continuous distributions of binding strengths. These results suggest that mimicry of antigen structure by anti-Id might best be understood from a quantitative perspective, and that idiotopes intimately associated with binding sites display a broader range of variants than those not associated with binding sites. In addition, for one monoclonal anti-Id recognizing a distal determinant, changing the radiolabeled proband in inhibition radioimmunoassays results in dramatic changes in relative inhibitory efficacies for certain anti-GAC antibody inhibitors. This observation suggests the possibility that this anti-Id represents an example of a multispecific (polyfunctional) anti-idiotypic antibody.
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NS
Greenspan
J M
JM
Davie
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology*; D001666:Binding Sites, Antibody; D000939:Epitopes; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D051381:Rats; D013329:Structure-Activity Relationship
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D011135:Polysaccharides, Bacterial