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*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 lipohexapeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-seryl-lysyl-l ysyl- lysyl-lysine, which is a biocompatible, Th-epitopeindependent adjuvant. Eleven of 37 tested HLA-B*3501 binding peptides mounted a CTL response after three in vitro stimulations. 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), gagp19 (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.
Schönbach
C
C
Department of Tumor Biology, University of Tokyo, Japan.
Nokihara
K
K
Bangham
C R
CR
Kariyone
A
A
Karaki
S
S
Shida
H
H
Takatsu
K
K
Egawa
K
K
Wiesmüller
K H
KH
Takiguchi
M
M
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000138:chemical synthesis / Q000276:immunology*; D015683:Gene Products, gag / Q000138:chemical synthesis / Q000276:immunology*; D015684:Gene Products, pol / Q000138:chemical synthesis / Q000276:immunology*; D016356:Gene Products, tax / Q000138:chemical synthesis / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D000956:Antigens, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D016356:Gene Products, tax; D015235:HLA-B Antigens; D010455:Peptides; D015682:Retroviridae Proteins, Oncogenic; D054301:gag Gene Products, Human Immunodeficiency Virus; C055266:gp46 protein, Human T-cell leukemia virus type I; C060955:p19 protein, Human T-lymphotropic virus 1