The effect of orientation of epitopes on the immunogenicity of chimeric synthetic peptides representing measles virus protein sequences

Mol Immunol. 1992 May;29(5):651-8. doi: 10.1016/0161-5890(92)90202-9.

Abstract

We have studied the influence of the orientation of T- and B-cell epitopes on the immunogenicity of chimeric synthetic peptides in terms of the ability of the T-cell epitope to provide help for the production of antibody to the B-cell epitope. A T-cell epitope from the fusion protein of measles virus (288-302), previously shown to act as a T-helper epitope in a panel of six inbred mouse strains, was co-linearly synthesized at either the amino- or carboxyl- terminus of a B-cell epitope from the haemagglutinin of the virus (188-199) with or without the inclusion of a glycine-glycine spacer. The four chimeric peptides were used to immunize a panel of five mouse strains and induced good anti-chimera antibody responses. In general, the chimeras in which the T-cell epitope was amino-terminal to the B-cell epitope induced antibodies which bound well to the B-cell epitope whereas the carboxyl-terminal orientation of the T-cell epitope with respect to the B-cell epitope failed to induce such antibody. These latter chimeras induced the production of antibodies which preferentially bound to the T-cell epitope. The inclusion of the gly-gly spacer in the chimeras did not enhance their immunogenicity nor did it increase antibody titres to the B-cell epitope. The affinity of the anti-peptide antibodies was markedly influenced by the orientation of the epitopes in the chimeras. The antibody elicited by the peptide in which the T-cell epitope was amino terminal to the B-cell epitope had significantly higher affinity for the B-cell epitope than that induced by immunization with the peptide in the reverse orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology
  • Epitopes*
  • Female
  • Measles virus / immunology*
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Protein Conformation
  • T-Lymphocytes / immunology
  • Viral Proteins / immunology*

Substances

  • Epitopes
  • Peptide Fragments
  • Viral Proteins