E6 and E7 fusion immunoglobulin from human papilloma virus 16 induces dendritic cell maturation and antigen specific activation of T helper 1 response

Biotechnol Lett. 2011 Apr;33(4):663-71. doi: 10.1007/s10529-010-0489-0. Epub 2010 Dec 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Dendritic Cells* / cytology
  • Dendritic Cells* / drug effects
  • Flow Cytometry
  • Human papillomavirus 16 / genetics*
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / pharmacology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / pharmacology*
  • Papillomavirus E7 Proteins / pharmacology*
  • Recombinant Fusion Proteins / pharmacology*
  • Repressor Proteins / genetics
  • Repressor Proteins / pharmacology*
  • Th1 Cells* / drug effects
  • Th1 Cells* / immunology

Substances

  • E6 protein, Human papillomavirus type 16
  • Immunoglobulins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins