title: In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
abstract: 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.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Sagar
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Shet
authors.initials: S
authors.lastname: Masih
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Schell
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
authors.affiliation: Immunotope, Inc., Doylestown, PA, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Comber
authors.affiliation: Immunotope, Inc., Doylestown, PA, USA.
authors.forename: Ramila
authors.initials: R
authors.lastname: Philip
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: pooja.jain@drexelmed.edu.
authors.forename: Pooja
authors.initials: P
authors.lastname: Jain
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: zkhan@drexelmed.edu.
authors.forename: Zafar K
authors.initials: ZK
authors.lastname: Khan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015490:HTLV-I Infections / Q000517:prevention & control*; D016056:Immunodominant Epitopes / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016212:Transforming Growth Factor beta / Q000097:blood; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D016356:Gene Products, tax; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014765:Viral Vaccines; C514970:tax protein, Human T-lymphotrophic virus 1
keywords: CD11c-DTR transgenic mice; Dendritic cells; HLA-A2.1 transgenic mice; HTLV-1; Tax
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