Analysis of antibody-antigen and antibody-anti-(idiotypic antibody) cross-reactivity using synthetic peptide probes.

The extent, nature and structural basis of immunological cross-reactivity of an anti-synthetic peptide monoclonal antibody (MAb) with the parent antigen (influenza virus haemagglutinin) from which the peptide was derived, and with a paratope-directed anti-idiotypic (anti-Id) antibody was investigated. Use of synthetic homologs and analogs of the peptide indicated that the anti-peptide MAb utilizes a common binding site to complex with peptide, haemagglutinin (HA) and anti-Id antibody, and the affinity constants for the binding of the anti-peptide MAb to peptide and to the anti-Id MAb were found to differ only by three fold. Determination of the amino acid sequence of the heavy chain variable domain (VH) of the anti-Id MAb did not reveal any obvious sequence homology with the peptide. Consideration of the spatial arrangement of residues, however, disclosed a region within the framework of the anti-Id VH with similarity to the epitope recognized by the anti-peptide MAb. This region, formed from antiparallel chains, contains amino acid residues arranged in a conformation similar to that assumed by amino acid residues comprising the epitope within the intact HA.