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Genome-Wide Approach to the CD4 T-Cell Response to Human Herpesvirus 6B.
Hanson, Derek J; Tsvetkova, Olga; Rerolle, Guilhem F; Greninger, Alexander L; Sette, Allesandro; Jing, Lichen; Campbell, Victoria L; Koelle, David M.
  • Hanson DJ; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Tsvetkova O; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Rerolle GF; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Greninger AL; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Sette A; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Jing L; Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
  • Campbell VL; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, California, USA.
  • Koelle DM; Department of Medicine, University of California-San Diego, La Jolla, California, USA.
J Virol ; 93(14)2019 07 15.
Article en En | MEDLINE | ID: mdl-31043533
ABSTRACT
Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) are population-prevalent betaherpesviruses with intermittent lytic replication that can be pathogenic in immunocompromised hosts. Elucidation of the adaptive immune response is valuable for understanding pathogenesis and designing novel treatments. Knowledge of T-cell antigens has reached the genome-wide level for CMV and other human herpesviruses, but study of HHV-6 is at an earlier stage. Using rare-cell enrichment combined with an HLA-agnostic, proteome-wide approach, we queried HHV-6B-specific CD4 T cells from 18 healthy donors with each known HHV-6B protein. We detected a low abundance of HHV-6-specific CD4 T cells in blood; however, the within-person CD4 T-cell response is quite broad the median number of open reading frame (ORF) products recognized was nine per person. Overall, the data expand the number of documented HHV-6B CD4 T-cell antigens from approximately 11 to 60. Epitopes in the proteins encoded by U14, U90, and U95 were mapped with synthetic peptides, and HLA restriction was defined for some responses. Intriguingly, CD4 T-cell antigens newly described in this report are among the most population prevalent, including U73, U72, U95, and U30. Our results indicate that selection of HHV-6B ORFs for immunotherapy should consider this expanded panel of HHV-6B antigens.IMPORTANCE Human herpesvirus 6 is highly prevalent and maintains chronic infection in immunocompetent individuals, with the potential to replicate widely in settings of immunosuppression, leading to clinical disease. Antiviral compounds may be ineffective and/or pose dose-limiting toxicity, and therefore, immune-based therapies have garnered increased interest in recent years. Attempts at addressing this unmet medical need begin with understanding the cellular response to HHV-6 at the individual and population levels. The present study provides a comprehensive assessment of HHV-6-specific T-cell responses that may inform the development of cell-based therapies directed at this virus.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Sistemas de Lectura Abierta / Herpesvirus Humano 6 / Epítopos de Linfocito T / Infecciones por Roseolovirus / Antígenos Virales Límite: Humans Idioma: En Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Sistemas de Lectura Abierta / Herpesvirus Humano 6 / Epítopos de Linfocito T / Infecciones por Roseolovirus / Antígenos Virales Límite: Humans Idioma: En Año: 2019 Tipo del documento: Article