Modification of the anchor residue to MHC class 1 augments CTL-inducing ability of epitope peptides derived from dengue virus NS3 protein / Hideyuki Masaki, Yoshiki Fujii, Kiyohiro Irimajiri, Hiroshi Munakata, Takanori T. Tomura, Ichiro Kurane

The residue (M) at the C-terminus of the original cytotoxic T lymphocyte (CTL) epitope peptide Den2.4 (GYISTRVEM) spinning the amino acid residues 298-306 of NS3 of dengue virus types 2 and 4 was substituted for L to prepare the peptide Den2.4-91, with a complete H-2K-binding motif. Similarly, the peptide Den1.3-91 with the binding motif was prepared from dengue virus types 1 and 3. In the present study, we investigated whether immunization with the corresponding CTL epitope peptide of the different serotype dengue virus induces specific cytotoxic T lymphocytes (CTLs). Subcutaneous immunization of BALB/c mice with Den1.3-9L emulsified with complete Freund adjuvant (CFA) induced the CTLs which lysed the target cells (P815) pulsed with peptide Den1.3-91 as well as those pulsed with peptide Den1.3 corresponding to the amino acid residues 299-307 (GYISTRVGM) of NS3 of dengue virus serotypes 1 and 3. Immunization with peptide Den1.3 did not induce CTLs in vivo, Furthermore, immunization with the peptide Den1.3-91 emulsified with incomplete Freund adjuvant (IFA) induced CTLs with less non-specific cytotoxicity. These results indicate that modification of dengue virus-derived CTL epitope peptide for providing the complete MHC class I binding motif augments the immunogenicity to induce specific CTLs.

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