The delineation of peptides able to mimic assembled epitopes.

Present methods allow a detailed study of the immune system's recognition of sequential epitopes. The results so far suggest that peptides homologous with these epitopes may not fulfil the early promise of synthetic vaccines. A procedure is described which now allows the study and evaluation of assembled epitopes. Using a monoclonal antibody which had been shown both to strongly neutralize foot-and-mouth disease virus, and to bind to a discontinuous epitope, peptides mimicking this epitope were determined a priori. An iterative procedure based on the progressive identification of amino acids in a random mixture of antibody-binding octapeptides was used. Strongly binding peptides consisted of the two elements W-Q-M (Trp-Gln-Met) and H-S (His-Ser) separated by a spacer. It was also shown that element W-Q-M was best composed of D-isomers, and the element H-S of L-isomers. Comparison of the sequence of these peptides with that of the immunologically important coat protein of the virus leads to the prediction that the epitope recognized by this monoclonal antibody consists of the residues occurring at positions 29-30, 54-55 and 88. Application of this general approach will answer questions about the nature of discontinuous epitopes and the stereochemical requirements for antigen-antibody interactions, as well as defining useful peptide immunogens.