Structural properties of chimeric peptides containing a T-cell epitope linked to a fusion peptide and their importance for in vivo induction of cytotoxic T-cell responses.
We have previously shown that when administered to mice without adjuvant, a chimeric peptide consisting of the fusion peptide F from measles virus protein linked at the C-terminus of a cytotoxic T-cell epitope from the M2 protein of respiratory syncytial virus efficiently primes for an major histocompatibility complex (MHC) class-I restricted cytotoxic T lymphocyte (CTL) response. In this report, we demonstrated by microspectrofluorometry that the fusion-peptide moiety bound to the plasma membrane of living cells. When the fusion peptide was linked to the C-terminus of the CTL epitope, the chimeric peptide (M2-F) adopted a marked beta-sheet conformation. In contrast, when the fusion peptide was linked to the N-terminus of the T-cell epitope (F-M2), the chimeric peptide adopted an alpha-helical conformation in the presence of trifluoroethanol. The immunogenicity of the two chimeric peptides for class-I restricted CTL was also significantly different, the one adopting the alpha-helical conformation being more immunogenic. Probably due to its obvious conversion to an alpha-helical conformation, the F-M2 peptide could have a higher propensity to insert into membranes, as shown by microspectrofluorometry, with a resultant better immunogenicity than the M2-F peptide.
Lelièvre
D
D
Centre de Biophysique Moléculaire, UPR 4301 CNRS, Orléans, France.
Hsu
S C
SC
Daubos
P
P
Favard
C
C
Vigny
P
P
Trudelle
Y
Y
Steward
M W
MW
Delmas
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D002942:Circular Dichroism; D000939:Epitopes / Q000276:immunology; D005260:Female; D015707:HN Protein; D007114:Immunization; D008459:Measles virus; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D012136:Respiratory Syncytial Viruses; D013050:Spectrometry, Fluorescence; D013154:Spleen; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014270:Trifluoroethanol / Q000494:pharmacology; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D015707:HN Protein; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G; D014270:Trifluoroethanol