Studies on in Vivo Induction of Cytotoxic T Lymphocyte Responses by Synthetic Peptides from E6 and E7 Oncoproteins of Human Papillomavirus Type 16

Abstract

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, V10C, with 9 of 10 amino acids overlapping with Q15L peptide (aa 49–58) to be capable of inducing CTLs against both V10C 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.