Structural features of a chimeric peptide inducing cytotoxic T lymphocyte responses in saline.
Little information is available correlating the structural properties of peptides with their immunogenicity in terms of responses via cytotoxic T lymphocytes (CTLs). The TT-NP6 chimeric peptide, consisting of two copies of a promiscuous T-helper epitope (T: residues 288-302 from the fusion protein of the measles virus) linked to the NP6 T-cytotoxic epitope (NP6: residues 52-60 from the nucleoprotein of measles virus) was able to induce virus-specific CTL responses in the absence of any adjuvant and hydrophobic component. The present work was undertaken to gain insight into structural features of the TT-NP6 peptide that may be important in optimizing the CTL immunogenicity of the peptide. Circular dichroism data, obtained in a buffer of physiological ionic strength and pH, strongly suggest a self-associated state for the peptide, which was confirmed by a sedimentation velocity experiment. However, helix association is accompanied by loss of overall helical content. Thermal-dependence studies show that the unfolding of self-associated alpha-helices is significantly more pronounced than the unfolding of isolated alpha-helices. Circular dichroism data, together with tryptic limited proteolysis, suggest the presence of a charged amino acid within the hydrophobic core. This study should provide a basis for engineering more effective immunogenic peptides against the measles virus by increasing the stability of the TT-NP6 peptide.
Delmotte
C
C
Centre de Biophysique Moléculaire, CNRS, UPR 4301, affiliée à l'Université d'Orléans, France.
Le Guern
E
E
Trudelle
Y
Y
Delmas
A
A
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry*; D006358:Hot Temperature; D013058:Mass Spectrometry; D008459:Measles virus / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010710:Phosphates / Q000494:pharmacology; D011489:Protein Denaturation; D017433:Protein Structure, Secondary / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000276:immunology; D012965:Sodium Chloride / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000737:chemistry* / Q000276:immunology; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000276:immunology
D000939:Epitopes; D019590:Nucleocapsid Proteins; D010446:Peptide Fragments; D010710:Phosphates; D011993:Recombinant Fusion Proteins; C400204:TT-NP6 protein, chimeric; D014758:Viral Core Proteins; D014760:Viral Fusion Proteins; D012965:Sodium Chloride