Investigations into the crossreactivity of rabbit antibodies raised against nonhomologous pairs of synthetic peptides derived from HIV-1 gp120 proteins

The immunological cross-reactivity of several peptides with specific patter n-property characteristics related to the epitopes of human immunodeficienc y virus type 1 (HIV-1) gp160/120 envelope proteins has been investigated. P roteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may crossreact with antibodies derived from the immunisation of animals with other member s of the same protein family. These structure-function characteristics may be revealed as periodicities derived from presentations based on the discre te Fourier transformation of the distributions of Various physico-chemical amino acid descriptors, constituting the polypeptide backbone and amino aci d side-chains of the protein molecule. Such approaches, for example, have p ermitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic alpha-helices and beta-sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this app roach, characteristic periodicities have been identified which represent co mmon Fourier transform spectral properties of the envelope (ENV) gp160/120 glycoproteins from a range of HIV-1 isolates, in addition, similar periodic ities have been detected as components of the discrete Fourier transform re presentation of the corresponding amino acid descriptors of the CD4 binding domain of gp120. Accordingly we have synthesised several peptides having p eriodic characteristics in their discrete Fourier transform representations similar to these HIV-1 proteins. These nonhomologous synthetic peptides in duced cross-reactive antibodies in New Zealand White rabbits. Polyclonal an tibodies raised to one of these peptides reacted with HIV-1 ENV gp120-relat ed proteins, as determined by enzyme-linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross-reactivity and molecular biomimicry in the development of peptide-based vaccines directed against viral or bacterial pathogens.