Studies on in vivo induction of cytotoxic T lymphocyte responses by synthetic peptides from E6 and E7 oncoproteins of human papillomavirus type 16

• Published in: Viral immunology Vol. 8; no. 3; p. 165
• Main Authors: Sarkar, A K, Tortolero-Luna, G, Nehete, P N, Arlinghaus, R B, Mitchell, M F, Sastry, K J
• Format: Journal Article
• Language: English
• Published: United States 1995
• Subjects: Amino Acid Sequence; Animals; Cytotoxicity, Immunologic - drug effects; Lymphocyte Activation - drug effects; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Oncogene Proteins, Viral - immunology; Papillomaviridae - immunology; Papillomavirus E7 Proteins; Peptides - chemical synthesis; Peptides - immunology; Peptides - pharmacology; Repressor Proteins; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0882-8245
• DOI: 10.1089/vim.1995.8.165

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.