Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells.
Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immunization of mice against lethal virus infection. To study whether this approach can be successful against virus-induced tumors we generated a B6 (H-2b) tumorigenic cell line transformed by human papillomavirus (HPV). This virus is detected in over 90% of all human cervical cancers. To identify vaccine candidates, we generated a set of 240 overlapping peptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. These peptides were tested for their ability to bind H-2Kb and H-2Db MHC class I molecules. Binding peptides were compared with the presently known peptide-binding motifs for H-2Kb and H-2Db and the predictive value of these motifs is shortly discussed. The high-affinity H-2Db-binding peptide and putative CTL epitope E7 49-57 (RAHYNIVTF) was used in vaccination studies against HPV 16-transformed tumor cells. Immunization with peptide E7 49-57 rendered mice insensitive to a subsequent challenge with HPV 16-transformed tumor cells in vivo, and induced a CTL response which lysed the tumor cells in vitro.
Feltkamp
M C
MC
Department of Immunohematology and Blood bank, University Hospital Leiden, The Netherlands.
Smits
H L
HL
Vierboom
M P
MP
Minnaar
R P
RP
de Jongh
B M
BM
Drijfhout
J W
JW
ter Schegget
J
J
Melief
C J
CJ
Kast
W M
WM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D000939:Epitopes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments / Q000276:immunology*; D012097:Repressor Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014412:Tumor Virus Infections / Q000517:prevention & control*; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*
C068651:E6 protein, Human papillomavirus type 16; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16