Studies on in vivo induction of cytotoxic T lymphocyte responses by synthetic peptides from E6 and E7 oncoproteins of human papillomavirus type 16.
Induction of cytotoxic T lymphocyte (CTL) responses is an important defense mechanism against infectious agents, specifically viruses. In the present investigation we employed a mouse assay system we previously developed, for rapid induction of CTLs by synthetic peptides from E6 and E7 oncoproteins of human papillomavirus type 16 (HPV-16). In particular, we compared the efficiency of CTL induction by HPV-16 peptides synthesized as linear monomers with those containing a dipalmitoyl-lysine-glycine-glycine (P2-KGG) moiety at the amino-terminus. Our results identified a 15-amino-acid peptide from E6(Q15L, aa 43-57) to be capable of inducing CTLs in vivo and addition of the lipid tail significantly increased CTL induction over that seen with the linear form of the peptide. Further, we identified a shorter peptide, V1OC, with 9 of 10 amino acids overlapping with Q15L peptide (aa 49-58) to be capable of inducing CTLs against both V1OC and Q15L. In case of E7 protein, our results demonstrated usefulness of P2-KGG moiety for enhanced CTL induction by previously identified CTL epitope peptides Q19D (aa 44-62) and R9F (aa 49-57). CTLs induced by both the E6 and E7 peptides were MHC class I-restricted and exhibited strict allele specificity and CD8+ phenotype. Our results showing enhanced cell-mediated immune responses with lipid-tailed forms of peptides add strength to the concept of a synthetic peptide-based vaccine for prophylaxis and therapy of HPV-associated cervical cancer.
Sarkar
A K
AK
Department of Veterinary Sciences, University of Texas M.D. Anderson Cancer Center, Bastrop, Texas 78602, USA.
Tortolero-Luna
G
G
Nehete
P N
PN
Arlinghaus
R B
RB
Mitchell
M F
MF
Sastry
K J
KJ
D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology*; D012097:Repressor Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16