Human Papillomavirus 16 E7-Specific Cytotoxic Lymphocyte Induction Through Mouse B7-1 Costimulating With E7 Of HPV16 Or E7C Subgene Fragment

Human papillomaviruses (HPV), which are important infectious agents, play a role in induction of proliferative or even malignant changes of human epidermis and mucosa. Those with tropism of mucosa are divided into " low risk" and "high risk" groups according to their relation to benign or malignant neoplasia respectively. HPV16, the most important member in "high risk" group, is capable of inducing precancer and even cancer of cervix; Previous studies have unambiguously shown that HPV16 E7 is the major transformational gene, and the expression of E7 is necessary for the maintenance of malignancy of cancer cells. The data from epidemiological investigation also show: HPV16 E7-oncoprotein is able to elicit immunoresponses in infected population; therefore, E7 is the ideal antigen suitable for preparation of prophylactic or therapeuticvaccine.The risks of inducing transformation exclude the E7 gene or E7 oncoprotein from being directly used as vaccine, therefore, to eliminate transformational activity and to retain the antigenicity of E7 have to be accomplished before E7 is designed as vaccine. It has been reported recently that the antigenic epitopes of E7 are mainly located at C-terminal of E7 (E7C) and transformation-associated regions are mainly at N-terminal. So it is a rational design in our research tentatively to develop vaccine with E7C terminal.In conformation with the theories of MHC class I -restricted antigen presentation and of two-signals activating T cell, direct inoculation of naked DNA into muscle is applied in our experiment in order that E7 is translated in vivo and E7 epitopes presented in context of MHC class I offering antigen-specific signal (signal 1) to CTL;...