Identification of HTLV-1-Specific CTL Directed against Synthetic and Naturally Processed Peptides in HLA-B3501 Transgenic Mice

• Published in: Virology (New York, N.Y.) N.Y.), 1996-12, Vol.226 (1), p.102-112
• Main Authors: Schönbach, Christian, Nokihara, Kiyoshi, Bangham, Charles R.M., Kariyone, Ai, Karaki, Sachiko, Shida, Hisatoshi, Takatsu, Kiyoshi, Egawa, Kohji, Wiesmüller, Karl-Heinz, Takiguchi, Masafumi
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antigens, Viral - immunology; Female; gag Gene Products, Human Immunodeficiency Virus; Gene Products, env - chemical synthesis; Gene Products, env - immunology; Gene Products, gag - chemical synthesis; Gene Products, gag - immunology; Gene Products, pol - chemical synthesis; Gene Products, pol - immunology; Gene Products, tax - chemical synthesis; Gene Products, tax - immunology; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Human T-lymphotropic virus 1 - immunology; Humans; Mice; Mice, Inbred C3H; Mice, Inbred ICR; Mice, Transgenic; Peptides - chemical synthesis; Peptides - immunology; Retroviridae Proteins, Oncogenic - chemical synthesis; Retroviridae Proteins, Oncogenic - immunology; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1996.0632

Previous studies of CTL responses to influenza peptides in HLA single transgenic mice resulted in the identification of at most one immunodominant epitope. Since HLA-B*3501 is known to present multiple HIV-1-specific T cell epitopes we tested the cellular immune response of HLA-B*3501 transgenic mice to synthetic HTLV-1 peptides mixed with the lipohexapeptideN-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-seryl-lysyl-lysyl-lysyl-lysine, which is a biocompatible, Th-epitope-independent adjuvant. Eleven of 37 tested HLA-B*3501 binding peptides mounted a CTL response after threein vitrostimulations. The HLA-B*3501 affinity of peptides correlated with their ability to induce CTL in HLA-B*3501 transgenic mice. Seven peptides derived from env-gp46 (VPSPSSTPLL, VPSSSSTPL, YPSLALAPH, and YPSLALAPA), pol (QAFPQCTIL), gag-p19 (YPGRVNEIL), and tax (GAFLTNVPY) proteins induced peptide-specific CTL. Bulk CTL generated by four peptides derived from env-gp46 (SPPSTPLLY, VPSPSSTPLLY, and VPSPSSTPLL) and pol (QAFPQCTILQY) killed peptide-pulsed and recombinant vaccinia-infected target cells. The latter peptides therefore present T-cell epitopes and are vaccine candidates for our transgenic mouse model.