The competitive inhibition of binding to overlapping epitopes has been described for antibodies to ACE.
None of the second injections resulted in a signal significantly above the plateau reached with the first injection, suggesting that all anti-GFP DARPins bind to overlapping GFP epitopes (supplementary material Fig. S6).
Finally, we performed epitope binning experiments to determine whether the selected DARPins bind to overlapping or to different epitopes on their respective target protein.
We opted to combine overlapping epitopes into peptides up to 20 aa in length.
Binding of mAbs to a region of overlapping epitopes for mAbs 9B9, 3G8, and i1A8 [32], [43], [43] visibly increased, whereas binding of mAbs 1G12 and 6A12 whose epitopes also overlap [15], [30] decreased.
Antibodies that bind to epitopes overlapping the CD4-binding site (CD4bs) on gp120 can prevent HIV entry by competing with cell-associated CD4; their ability to outcompete CD4 is a major determinant of their neutralizing potency and is proportional to their avidity.
RSV-C4 and RSV-D3 bound to the same mutants with some small differences, possibly due to differences in affinity or recognition of overlapping epitopes.
The challenge would be to immunize with a large enough cocktail of overlapping epitopes.
Overlapping epitopes are defined as those that share >30% of the same residues with respect to the epitope with the higher epitope score.
The only pan-ebolavirus neutralizing Abs reported thus far target overlapping epitopes in the viral IFL21,23,24,25,26.
