Human herpesvirus-6B (HHV-6B) is a ubiquitous pathogen with frequent reactivation observed in immunocompromised patients such as bone marrow 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 cytomegalovirus (CMV) and Epstein-Barr virus (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 (IE1B) and presented by common HLA class I alleles including H... More
Human herpesvirus-6B (HHV-6B) is a ubiquitous pathogen with frequent reactivation observed in immunocompromised patients such as bone marrow 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 cytomegalovirus (CMV) and Epstein-Barr virus (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 (IE1B) and presented by common 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. This article is protected by copyright. All rights reserved.