Nastke, Maria-DorotheaBecerra, AniuskaYin, LiusongDominguez-Amorocho, OmarGibson, Laura LStern, Lawrence J.Calvo-Calle, J Mauricio2022-08-232022-08-232012-05-012012-06-20J Virol. 2012 May;86(9):4776-92. Epub 2012 Feb 22. doi: 10.1128/​JVI.06573-111098-551410.1128/​JVI.06573-1122357271https://hdl.handle.net/20.500.14038/43097Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4(+) T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-γ) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4(+) T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4(+) T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.en-USAntigens, ViralCD4-Positive T-LymphocytesCell LineCross ReactionsCytokinesEpitopes, T-LymphocyteHLA-DR1 AntigenHaplotypesHerpesvirus 6, HumanHumansInterferon-gammaLeukocytes, MononuclearPeptidesProtein MultimerizationRoseolovirus InfectionsT-LymphocytesT-Lymphocytes, CytotoxicTissue DonorsViral LoadImmunology and Infectious DiseasePathologyVirologyJournal Articlehttps://escholarship.umassmed.edu/pathology_pp/153009999pathology_pp/15