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 language | English (US) |
|---|---|
| Pages (from-to) | 3573-3584 |
| Number of pages | 12 |
| Journal | European Journal of Immunology |
| Volume | 44 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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Keywords
- CD8 T cells
- HHV-6
- Immediate-early 1 protein
- Immunotherapy
- Infectious disease
- Virology
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
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. / Iampietro, Mathieu; Morissette, Guillaume; Gravel, Annie; Dubuc, Isabelle; Rousseau, Matthieu; Hasan, Aisha; O'Reilly, Richard J.; Flamand, Louis.
In: European Journal of Immunology, Vol. 44, No. 12, 2014, p. 3573-3584.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Iampietro, Mathieu
AU - Morissette, Guillaume
AU - Gravel, Annie
AU - Dubuc, Isabelle
AU - Rousseau, Matthieu
AU - Hasan, Aisha
AU - O'Reilly, Richard J.
AU - Flamand, Louis
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - HHV-6
KW - Immediate-early 1 protein
KW - Immunotherapy
KW - Infectious disease
KW - Virology
UR - http://www.scopus.com/inward/record.url?scp=84908367477&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908367477&partnerID=8YFLogxK
U2 - 10.1002/eji.201444931
DO - 10.1002/eji.201444931
M3 - Article
C2 - 25243920
AN - SCOPUS:84908367477
VL - 44
SP - 3573
EP - 3584
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 12
ER -