# HPV AND ANTIGEN PRESENTING CELLS

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $420,544

## Abstract

Project Summary
Human papillomaviruses (HPV) are common sexually transmitted viruses and their infections are a significant
health burden for the population. Persistent infection with high-risk HPV genotypes result in the development of
a variety of human cancers, most prominently cervical, anal, and subtypes of head and neck cancers. HPV
establishes persistent infection within the host through evasion of the immune system. One of the ways HPV
accomplishes this is by manipulating Langerhans cells (LC), which are the antigen presenting cells at the site
of infection that are responsible for initiating immune responses against epithelium invading viruses. The
interaction of HPV with LC through the annexin A2 heterotetramer (A2t) and subsequent suppressive signaling
events act as a braking mechanism that stops LC activation, resulting in incomplete LC maturation and
prevention of an effective antiviral T cell immune response. Our long-term goals are to understand how HPV
manipulates LC activation and antigen processing to evade the immune system and test new ways to treat
HPV-associated diseases. AIM 1 will focus on the effects of utilizing a “brakes off, gas pedal down”
combination approach for activating LC exposed to HPV. This will be investigated through cell surface marker
and cytokine analysis and functional immunological assays. AIM 2 will investigate the signaling pathways and
A2t interaction partners associated with A2t-mediated suppression of LC immune function that are hijacked by
HPV using biochemical and cell biological approaches. This will be analyzed through broad interrogation of
phosphoprotein activation and cell signaling networks, antigen presenting cell specific profiling gene arrays,
and a newly developed Single Molecule Pulldown (SiMPull) assay. AIM 3 will evaluate the contribution of A2t
to LC Birbeck granule structure, function, and role in HPV antigen processing. This will be investigated through
immuno-electron microscopic analysis of Birbeck granule components in LC, assessment of A2t protein
knockdown effects on Birbeck granule formation, and elucidation of the effects of protein knockdown on the
ability of LC to properly process and present HPV-derived peptides to HLA-matched T cell clones. Additionally,
these aims will utilize innovative skin explant and 3-D culture systems to validate that the proposed HPV16-A2t
interactions are important for LC biology in vivo. Collectively the proposed studies will provide deep insight into
basic LC biology and function. In addition we will examine the effects of a novel two-pronged approach focused
on preventing negative signaling events in LC while simultaneously providing a positive stimulus to activate LC
as a novel strategy to treat HPV infections, thereby preventing HPV-associated cancers.

## Key facts

- **NIH application ID:** 9978719
- **Project number:** 5R01CA074397-20
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** WIJBE MARTIN KAST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,544
- **Award type:** 5
- **Project period:** 1997-06-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978719

## Citation

> US National Institutes of Health, RePORTER application 9978719, HPV AND ANTIGEN PRESENTING CELLS (5R01CA074397-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978719. Licensed CC0.

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