Structural requirements for synthetic immunogens to induce measles virus specific CTL responses.
We have studied the immunogenicity of a synthetic peptide representing a cytotoxic T cell epitope (CTL) from the nucleoprotein of measles virus (MV). For the induction of peptide and MV-specific CTL responses after subcutaneous immunization, covalent linkage of the CTL epitope to a T-helper epitope was required. The presence of two copies of the T-helper epitope at the amino terminus of the CTL epitope (TT-CTL) resulted in the induction of strong CTL responses after administration in saline. In contrast, a chimeric peptide with one copy of the T-helper epitope at the amino terminus of the CTL epitope (T-CTL) was weakly immunogenic when given in saline. Analysis of the structure of the TT-CTL chimeric peptide by CD spectroscopy revealed an alpha-helical conformation, as compared to the random coil conformation favored by the T-CTL chimeric peptide. In addition, the CD spectra of the TT-CTL peptide in the presence of small unilamellar vesicules (SUV) revealed an increased helicity, as compared to the spectra of the T-CTL chimera in the presence of SUV. This suggests that the amphipathic character of the TT-CTL chimeric construct favors its interaction with the cell membrane of antigen presenting cells, therefore, facilitating its cytosolic delivery for class I presentation. These findings highlight the importance of antigen structure for the in vivo induction of CTL responses and may have implications for the design of synthetic peptide vaccines.
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Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, U.K.
Delmas
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Steward
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D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology*; D002942:Circular Dichroism; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D008213:Lymphocyte Activation; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D015335:Molecular Probes; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014758:Viral Core Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D015335:Molecular Probes; D010455:Peptides; D014758:Viral Core Proteins