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Adenovirus hexon T-cell epitope is recognized by most adults and is restricted by HLA DP4, the most common class II allele

Gene Therapy volume 11, pages 1408–1415 (2004)Cite this article

Abstract

The immunogenicity of adenovirus (Ad) vectors is enhanced by virus-specific memory immune responses present in most individuals as a result of past exposure to these ubiquitous pathogens. We previously identified the first human T-cell epitope from the major capsid protein hexon, H910-924, and found that it is highly conserved among different Ad serotypes. Memory/effector T-cell responses to H910-924 were detected in 14 of 18 (78%) healthy adults by an interferon-γ ELISPOT assay. Hexon peptide-specific CD4 T-cell lines were generated from three HLA-typed donors and analyzed using a panel of HLA homozygous B-cell lines and monoclonal antibodies to HLA class II loci. These studies reveal that the hexon epitope is restricted by HLA DP4, a class II allele present in 75% of the population. Analysis of overlapping peptides and peptides with single residue mutations identified a HLA DP4-binding motif. Additionally, antibodies to the hexon peptide were detected in all donor sera by dot blot assay and ELISA. Therefore, most individuals exhibit both memory B- and T-cell responses to this highly conserved epitope on hexon, an obligate component of all Ad vectors, including ‘gutted’ vectors. These data suggest that current strategies for the use of Ad gene therapy vectors will not evade memory immune responses to Ad.

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Acknowledgements

We thank Dr D Eckels for the gift of the HLA homozygous B-cell lines. We especially thank all of the participants who donated blood for this study. This research was supported by grants from the National Institutes of Health (RO1 AI42842) and GlaxoSmithKline.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA

    J Tang, M Olive, K Champagne & L Eisenlohr

  2. Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA

    N Flomenberg & P Flomenberg

  3. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    N Flomenberg, L Eisenlohr & P Flomenberg

  4. American Red Cross, Philadelphia, PA, USA

    S Hsu

  5. Center of Human Virology, Thomas Jefferson University, Philadelphia, PA, USA

    P Flomenberg

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Tang, J., Olive, M., Champagne, K. et al. Adenovirus hexon T-cell epitope is recognized by most adults and is restricted by HLA DP4, the most common class II allele. Gene Ther 11, 1408–1415 (2004). https://doi.org/10.1038/sj.gt.3302316

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