title: 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.
abstract: Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen with frequent reactivation observed in immunocompromised patients such as BM transplant (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.
authors.affiliation: Division of Infectious Disease and Immunity, CHU de Quebec Research Center, Quebec City, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Iampietro
authors.forename: Guillaume
authors.initials: G
authors.lastname: Morissette
authors.forename: Annie
authors.initials: A
authors.lastname: Gravel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dubuc
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rousseau
authors.forename: Aisha
authors.initials: A
authors.lastname: Hasan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Louis
authors.initials: L
authors.lastname: Flamand
mesh_terms: D000293:Adolescent; D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D019349:Roseolovirus Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy
chemical_list: D018984:Epitopes, T-Lymphocyte; C524866:HLA-A*02 antigen; C487960:HLA-A*03 antigen; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; C425023:HLA-B*07 antigen; D015793:HLA-B7 Antigen; D017874:Immediate-Early Proteins
keywords: CD8 T cells; HHV-6; Immediate-early 1 protein; Immunotherapy; Infectious disease; Virology