Structure-immunogenicity relationship of melittin and its N-terminal truncated analogs.

Melittin is an amphipathic 26-residue peptide from bee venom. We showed previously that, in the murine system, melittin has one major B-cell epitope in the hydrophilic region of residues 21-26 and one T-cell epitope in the hydrophobic midregion of 11-19. In this paper we compared the immunogenicity and the biophysical properties of a series of melittin analogs which differ by stepwise two-residue truncation in the N-terminus of residues 2-10. All analogs retain the B- and T-cell epitopes of melittin. However, the analogs which have more than two residues deleted at the N-terminus are nonimmunogenic for antibody responses although they are immunogenic for T-cell responses. The analogs were found to differ in their hemolytic activity, helical content, and oligomer formation in different solvents. These results support the hypothesis that the immunogenicity of melittin for antibody response is associated with its binding to cell membranes followed with oligomer formation but its immunogenicity for T-cell response is not.