HPV type 16 protein E7 HLA-A2 binding peptides are immunogenic but not processed and presented

Human papillomaviruses (HPV) have been implicated in the etiology of cervic al malignancies and a high percentage of cervical carcinoma cells express H PV-16 E6 and E7 oncoproteins. These proteins are attractive targets for cyt olytic T lymphocyte (CTL) mediated immunotherapy. We screened peptides deri ved from the HPV-16 E7 protein for binding to HLA-A2 and rested their poten tial to induce specific CTL responses in chimeric HLA-A2/H2-Kb transgenic m ice. From eight potential binding peptides four displayed binding and were tested for immunogenicity. CTL activity was tested using target cells pulse d with peptide or expressing E7 protein. While there was no CTL induction o bserved with the peptides 7-15, 66-74 and 82-90; CTL From mice immunized wi th 86-93 lysed targets presenting the peptide in the context of the HLA-A2/ H2-Kb molecule or wild-type HLA-AZ. In contrast, 86-93 induced CTL showed n o cytolytic activity against cells expressing the protein E7 and vaccinatio n with the E7 protein did not lead to cytotoxicity against targets pulsed w ith the 86-93 peptide. Therefore the peptide 86-93, which binds to HLA-A2, is able to induce CTL responses in context of HLA-AZ, but the peptide appea rs not to be processed or presented by HPV type 16 infected cells. (C) 2000 Elsevier Science B.V. All rights reserved.