| Cervical cancer is one of the most common tumors of female. It is usually caused by human papillomavirus (HPV), especially by type16,18. The therapic vaccines aim at E6 and E7 have some curative effect. But recent research has found that: The immune react to E6 and E7 protein of HPV18 have no relation to the regression of pathological changes. This maybe ascribe to the proteins'later expressing in the infected cells. Conversely, E2 protein, in charge of regulating DNA replication and genome expression, express in the infected cells stably and abundantly in the early stage of disease.Cytotoxic T lymphocyte (CTL) plays a very important role in anti-tumor and anti-virus immune reaction. Stimulated by antigen and cytokine, the precursor cell proliferated and differentiated to specificity CTL. So, if we could induce effective CTL which specificity aimed at HPV18 E2 protein, we would found another key to cure HPV18 associated disease.But, the whole HPV18 E2 protein contains not only the CTL epitopes but also the B cell and Th cell epitopes. Those epitopes maybe inhibit each other and lead to the reduction of antigencity.The phenomenons of immune deviation and immune subvertion also suggested that the vaccine constructed by CTL epitopes maybe more excellent than the whole protein.The stability of"MHCâ… -peptide"compound is essentially to the activation of CTL. In our study, the methods to find out the CTL epitopes of E2 are based on this theory.Our study composes of two parts:Part 1 Synthesis of HPV18 E2 CTL epitopes,construction in hela cells of pIRES2- HPV18 E2-EGFP, function analysis of epitope-specifical CTL HPV18 E2 CTL epitopes were determined by quantization motif method, three peptides with the hightest total binding coefficient were selected as the candidate peptides. All the peptides were synthesized by ZC Biochem Ltd (Shanghai), using the method of Fmoc solid-phase synthesis on ABI-431A peptidesynthesizer. The sequence encoding for... |
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