title: E6 and E7 fusion immunoglobulin from human papilloma virus 16 induces dendritic cell maturation and antigen specific activation of T helper 1 response.
abstract: Human papilloma virus (HPV) 16 causes cervical cancer. Induction of oncogenesis by HPV 16 is primarily dependent on the function of E6 and E7 proteins, which inactivate the function of p53 and pRB, respectively. Thus, blocking the activity of the E6 and E7 proteins from HPV 16 is critical to inhibiting oncogenesis during infection. We have expressed and purified soluble HPV 16 E6 and E7 fusion immunoglobulin (Ig), which were combined with the constant region of an Ig heavy chain, in a mammalian system. To assess whether soluble E6 and E7 fusion Igs induce effective cellular immune responses, immature dendritic cells (DCs) were treated with these fusion proteins. Soluble E6 and E7 fusion Igs effectively induced maturation of DCs. Furthermore, immunization with soluble E6 and E7 fusion Igs in mice resulted in antigen-specific activation of T helper 1 (Th1) cells. This is the first comprehensive study to show the molecular basis of how soluble HPV 16 E6 or E7 fusion Igs induces Th1 responses through the maturation of DCs. In addition, we show that DC therapy using soluble HPV E6 and E7 fusion Igs may be a valuable tool for controlling the progress of cervical cancer.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Hur
authors.forename: Suk Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Yu-Koung
authors.initials: YK
authors.lastname: Oh
authors.forename: Woon-Won
authors.initials: WW
authors.lastname: Jung
authors.forename: Jong Bok
authors.initials: JB
authors.lastname: Seo
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Nam
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
authors.forename: Taehoon
authors.initials: T
authors.lastname: Chun
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000494:pharmacology*; D050725:Papillomavirus E7 Proteins / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D007136:Immunoglobulins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins