Cytotoxic T lymphocytes raised against a subdominant epitope offered as a synthetic peptide eradicate human papillomavirus type 16-induced tumors.
Previously, we have shown that immunization with human papillomavirus (HPV) type 16-derived cytotoxic T lymphocyte (CTL) epitope E7 49-57 (RAHYNIVTF) renders C57BL/6 mice insensitive to tumors formed by HPV16-transformed cells. In this study, we provide evidence that E7 49-57 is expressed as a subdominant CTL epitope on HPV16-transformed C57BL/6 cells. Using acid peptide elution, it is shown that HPV16-transformed cells express another CTL epitope, besides E7 49-57, which appears to be dominant. We demonstrate that a CTL line raised against the subdominant CTL epitope, offered as synthetic peptide E7 49-57, eradicates established HPV16-induced tumors in mice. Our data show that synthetic peptide-induced CTL can be applied successfully in vivo against (virus-induced) tumor, and emphasize that subdominant CTL epitopes are useful targets for immunotherapy. Furthermore, it is illustrated for the first time that HPV16-specific CTL interfere directly with HPV16-induced tumors.
Feltkamp
M C
MC
Department of Immunohematology, University Hospital Leiden, The Netherlands.
Vreugdenhil
G R
GR
Vierboom
M P
MP
Ras
E
E
van der Burg
S H
SH
ter Schegget
J
J
Melief
C J
CJ
Kast
W M
WM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D000939:Epitopes / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology*; D027383:Papillomaviridae / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology*
D000939:Epitopes; D010455:Peptides