Structural features of a chimeric peptide inducing cytotoxic T lymphocyte responses in saline

Little information is available correlating the structural properties of pe ptides with their immunogenicity in terms of responses via cytotoxic T lymp hocytes (CTLs). The TT-NP6 chimeric peptide, consisting of two copies of a promiscuous T-helper epitope (T: residues 288-302 from the fusion protein o f the measles virus) linked to the NP6 T-cytotoxic epitope (NP6: residues 5 2-60 from the nucleoprotein of measles virus) was able to induce virus-spec ific 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 immunogen icity of the peptide. Circular dichroism data, obtained in a buffer of phys iological ionic strength and pH, strongly suggest a self-associated state f or the peptide, which was confirmed by a sedimentation velocity experiment. However, helix association is accompanied by loss of overall helical conte nt. Thermal-dependence studies show that the unfolding of self-associated a lpha-helices is significantly more pronounced than the unfolding of isolate d alpha-helices. Circular dichroism data, together with tryptic limited pro teolysis, suggest the presence of a charged amino acid within the hydrophob ic core. This study should provide a basis for engineering more effective i mmunogenic peptides against the measles virus by increasing the stability o f the TT-NP6 peptide.