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  • Oral presentation
  • Open Access

In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.

  • 1,
  • 1,
  • 2,
  • 3,
  • 4,
  • 4,
  • 5,
  • 1 and
  • 1Email author
Retrovirology201512 (Suppl 1) :O28

https://doi.org/10.1186/1742-4690-12-S1-O28

  • Published:

Keywords

  • Asymptomatic Carrier
  • Vaccine Trial
  • CD8T Cell
  • Viral Oncoprotein
  • CD8T Cell Response

Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax (11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax (11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax (11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax (11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses.

Authors’ Affiliations

(1)
Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USA
(2)
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA
(3)
Viral Immunology Section, Neuroimmunology Branch, National Institutes of Health, Bethesda, MD, USA
(4)
Immunotope Inc., Doylestown, PA, USA
(5)
Department of Microbiology and Immunology, and the Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA

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