Journal article
In vivo immunogenicity of Tax(11–19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine
Vaccine, v 32(26), pp 3274-3284
30 May 2014
PMID: 24739247
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
•HLA-A2/DTR transgenic mouse strain was generated to study immunogenicity of Tax(11–19) epitope.•A reduced proliferation of CD8+ splenocytes from Tax(11–19) immunized DC-depleted mice is observed.•Adjuvant usage demonstrated higher frequency of Tax(11–19)-specific cells.•Tax(11–19) epitope can be a potential candidate for a DC-based anti-HTLV-1 vaccine.
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.
Metrics
Details
- Title
- In vivo immunogenicity of Tax(11–19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine
- Creators
- Divya Sagar - Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USAShet Masih - Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USATodd Schell - Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USASteven Jacobson - Viral Immunology Section, Neuroimmunology Branch, National Institutes of Health, Bethesda, MD, USAJoseph D Comber - Immunotope, Inc., Doylestown, PA, USARamila Philip - Immunotope, Inc., Doylestown, PA, USABrian Wigdahl - 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, USAPooja Jain - Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USAZafar K Khan - Department of Microbiology and Immunology, Drexel Institute for Biotechnology & Virology Research, Drexel University College of Medicine, Philadelphia, PA, USA
- Publication Details
- Vaccine, v 32(26), pp 3274-3284
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000336872500024
- Scopus ID
- 2-s2.0-84900395797
- Other Identifier
- 991014877956704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental