Recognition of a cervical cancer derived tumor cell line by a human papillomavirus type 16 E6 52-61-specific CD8 T cell clone.

The E6 and E7 proteins of high-risk human papillomavirus (HPV) types are thought to be the ideal sources of antigens for immunotherapy for cervical cancer since they are expressed by the tumors and not by normal cells. We recently described new HPV 16 epitopes, including the E6 52-61 peptide restricted by HLA class I molecule B57. Primary tumor cell lines were established from three HLA-B57 positive, HPV 16 positive cervical cancer patients, and their recognition by a E6 52-61 specific CD8+ T cell clone was determined using a chromium release assay and an IFN-gamma enzyme-linked immunospot (ELISPOT) assay. The recognition of homologous epitopes contained in other high-risk HPV types (18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73) was also examined at the peptide level. A low level of killing of two of the tumor cell lines derived from the three patients was demonstrated using a chromium release assay. The level of killing of one of these tumor cell lines was enhanced upon treatment with IFN-gamma and/or the addition of antigen. This tumor cell line also induced measurable IFN-gamma secretion. The recognition of homologous epitopes from HPV 35, 39, 45, 51, and 73 was detected in an ELISPOT assay. Therefore, the HPV 16 E6 52-61 epitope appears to be at least weakly expressed by tumor cell lines derived from cervical cancer, and the HPV 16 E6 52-61-specific T cell clone can recognize homologous peptides derived from other high risk HPV sequences.

RNA interference is an antiviral defence mechanism in Caenorhabditis elegans.

RNA interference (RNAi) is an evolutionarily conserved sequence-specific post-transcriptional gene silencing mechanism that is well defined genetically in Caenorhabditis elegans. RNAi has been postulated to function as an adaptive antiviral immune mechanism in the worm, but there is no experimental evidence for this. Part of the limitation is that there are no known natural viral pathogens of C. elegans. Here we describe an infection model in C. elegans using the mammalian pathogen vesicular stomatitis virus (VSV) to study the role of RNAi in antiviral immunity. VSV infection is potentiated in cells derived from RNAi-defective worm mutants (rde-1; rde-4), leading to the production of infectious progeny virus, and is inhibited in mutants with an enhanced RNAi response (rrf-3; eri-1). Because the RNAi response occurs in the absence of exogenously added VSV small interfering RNAs, these results show that RNAi is activated during VSV infection and that RNAi is a genuine antiviral immune defence mechanism in the worm.