Human herpesvirus 6B immediate-early I protein contains functional HLA-A*02, HLA-A*03, and HLA-B*07 class I restricted CD8+ T-cell epitopes

Mathieu Iampietro, Guillaume Morissette, Annie Gravel, Isabelle Dubuc, Matthieu Rousseau, Aisha Hasan, Richard J. O'Reilly, Louis Flamand

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen with frequent reactivation observed in immunocompromised patients such as BMtransplant (BMT) recipients. Adoptive immunotherapy is a promising therapeutic avenue for the treatment of opportunistic infections, including herpesviruses. While T-cell immunotherapy can successfully control CMV and EBV reactivations in BMT recipients, such therapy is not available for HHV-6 infections, in part due to a lack of identified protective CD8+ T-cell epitopes. Our goal was to identify CD8+ T-cell viral epitopes derived from the HHV-6B immediate-early protein I and presented by common human leukocyte Ag (HLA) class I alleles including HLA-A*02, HLA-A*03, and HLA-B*07. These epitopes were functionally tested for their ability to induce CD8+ T-cell expansion and kill HHV-6-infected autologous cells. Cross-reactivity of specific HHV-6B-expanded T cells against HHV-6A-infected cells was also confirmed for a conserved epitope presented by HLA-A*02 molecule. Our findings will help push forward the field of adoptive immunotherapy for the treatment and/or the prevention of HHV-6 reactivation in BMT recipients.

Original languageEnglish (US)
Pages (from-to)3573-3584
Number of pages12
JournalEuropean Journal of Immunology
Volume44
Issue number12
DOIs
StatePublished - Jan 1 2014

Keywords

  • CD8 T cells
  • HHV-6
  • Immediate-early 1 protein
  • Immunotherapy
  • Infectious disease
  • Virology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Iampietro, M., Morissette, G., Gravel, A., Dubuc, I., Rousseau, M., Hasan, A., O'Reilly, R. J., & Flamand, L. (2014). Human herpesvirus 6B immediate-early I protein contains functional HLA-A*02, HLA-A*03, and HLA-B*07 class I restricted CD8+ T-cell epitopes. European Journal of Immunology, 44(12), 3573-3584. https://doi.org/10.1002/eji.201444931