The effect of orientation of epitopes on the immunogenicity of chimeric synthetic peptides representing measles virus protein sequences.
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.
Partidos
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Department of Clinical Sciences, London School of Hygiene & Tropical Medicine, U.K.
Stanley
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Steward
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D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes; D005260:Female; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D000939:Epitopes; D010446:Peptide Fragments; D014764:Viral Proteins