Identification of HTLV-1-specific CTL directed against synthetic and naturally processed peptides in HLA-B*3501 transgenic mice

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(star)3501 is known to present multiple HIV-1-specific T cell epitopes we tested the cellular immune response of HLA-B(star)3501 transgenic mice to synthetic HTLV-1 peptides mixed with the lipohexapeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-seryl-lysyl-lysyl-lysyl-lysine, which is a biocompatible, T-h-epitope-independent adjuvant Eleven of 37 tested HLA-B(star)3501 binding peptides mounted a CTL response after three in vitro stimulations. The HLA-B(star)3501 affinity of peptides correlated with their ability to induce CTL in HLA-B(star)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. (C) 1996 Academic Press, Inc.