Can the antibody be polyclonal?
Maybe. A polyclonal antibody raised against a large antigen will likely contain numerous epitope specificities corresponding to different regions of the antigen and, if the antibody has not been affinity purified, other antigen specificities as well. When panning against such a heterogeneous population of antibodies, it is unlikely that a well-defined consensus epitope sequence will emerge. Rather, numerous sequences corresponding to the individual specificities will be selected, which will be difficult to discern against the background of non-binding sequences. For smaller antigens, the number of selected epitope sequences will likely be more manageable, particularly if the antibody is affinity purified. Experiments at New England Biolabs have demonstrated that polyclonal antibodies raised against peptide antigens yield clear consensus epitope sequences.
