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Impact of dendritic cells and adjuvant on the in vivo immunogenicity of HTLV-1 Tax 11-19 epitope in hybrid HLA-A2.1/DTR transgenic mice

  • 1,
  • 1,
  • 2,
  • 1,
  • 1 and
  • 1
Retrovirology201411 (Suppl 1) :P72

https://doi.org/10.1186/1742-4690-11-S1-P72

  • Published:

Keywords

  • Diphtheria Toxin
  • Viral Oncoprotein
  • Restricted Epitope
  • Transgenic Mouse Strain
  • Diphtheria Toxin Receptor

Individually, HLA-A2.1 and CD11c-DTR transgenic mouse strains have been used to investigate the immunopathogenesis of different viruses and have provided important insights into current understanding of host-pathogen interactions during human T-cell leukemia virus type 1 (HTLV-1) infection. Here, these mice enabled the study of the CD8 T-cell immune response against a known MHC class I HLA-A2.1-restricted epitope 11-19 of the viral oncoprotein Tax delivered along with tetanus helper peptide without or with incomplete Freund’s adjuvant (IFA) in the absence and presence of dendritic cells (DCs). First, a cross breeding strategy was utilized to generate a HLA-A2.1/DTR hybrid strain that carries an HLA-A2.1 gene and diphtheria toxin receptor gene for in vivo depletion of CD11c+ DCs. Upon in vitro stimulation of splenocytes from immunized mice with autologous bone marrow-derived DCs primed with Tax11-19 antigen, DC-depleted mice showed marked attenuation in the proliferation of CD8+ T-cells when compared with the non DC-depleted mice. Additionally, mice immunized with adjuvant demonstrated a much higher frequency of Tax11-19-specific cells response but overall reduced proliferation compared to the non-adjuvant group. A significantly high serum level of IL-6 coincided with depletion of DCs while a decrease in TGF-β cytokine associated with adjuvant use irrespective of DCs’ presence. In conclusion, these studies not only demonstrate that the clinically characterized Tax epitope 11-19 can be a potential candidate for the DC-based anti-HTLV-1 vaccine but also illustrate a broader application of the new HLA-A2.1/DTR-transgenic hybrid mouse strain as an important tool to investigate DC involvement in human class-I-restricted immune responses.

Authors’ Affiliations

(1)
Drexel Institute for Biotechnology and Virology Research, and the Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, USA
(2)
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA

Copyright

© Sagar et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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