Delayed-type hypersensitivity response to human papillomavirus type 16 E6 protein in a mouse model

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Human papillomavirus (HPV) infections are linked to epithelial cancers.
• Understanding the immune response to HPV oncoproteins like E6 is crucial for vaccine development.
• Existing models often do not fully replicate the epitheliotropic nature of HPV infections.

Purpose of the Study:

• To establish and validate a novel mouse model for studying in vivo immune responses to HPV type 16 (HPV-16) E6 protein.
• To investigate the cellular immune response, specifically delayed-type hypersensitivity (DTH), to HPV-16 E6.
• To assess the specificity of the immune response generated against HPV-16 E6.

Main Methods:

• Development of a novel immortal keratinocyte cell line expressing the HPV-16 E6 protein.
• Grafting of the E6-expressing keratinocytes onto syngeneic mice to create a differentiated epithelium.
• Induction of a delayed-type hypersensitivity (DTH) reaction by intradermal challenge with a recombinant vaccinia virus expressing HPV-16 E6.
• Assessment of immune response specificity using control viruses expressing HPV-16 E7 or L1 proteins.

Main Results:

• A significant delayed-type hypersensitivity (DTH) reaction was observed in grafted mice challenged with HPV-16 E6-expressing vaccinia virus.
• The DTH response was specific to the HPV-16 E6 protein.
• No DTH reaction was observed when mice were challenged with vaccinia virus expressing HPV-16 E7 or L1 proteins, confirming antigen specificity.

Conclusions:

• The developed mouse model effectively mimics the presentation of viral antigens in a manner analogous to natural HPV infection.
• The study demonstrates a specific in vivo cellular immune response (DTH) to the HPV-16 E6 oncoprotein.
• This model provides a valuable platform for further research into HPV immunity and the development of targeted immunotherapies or vaccines.