Article

Journal of Clinical Immunology

, Volume 30, Issue 5, pp 703-722

Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes

  • Kerry J. LaingAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center
  • , Amalia S. MagaretAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterDepartment of Laboratory Medicine, University of Washington
  • , Dawn E. MuellerAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center
  • , Lin ZhaoAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center
  • , Christine JohnstonAffiliated withDepartment of Laboratory Medicine, University of Washington
  • , Stephen C. De RosaAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterHIV Vaccine Trials Network, Fred Hutchinson Cancer Research CenterDepartment of Laboratory Medicine, University of WashingtonCenter for AIDS Research, University of Washington
  • , David M. KoelleAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterDepartment of Laboratory Medicine, University of WashingtonDepartment of Medicine, University of WashingtonDepartment of Global Health, University of WashingtonBenaroya Research Institute
  • , Anna WaldAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterDepartment of Laboratory Medicine, University of WashingtonDepartment of Epidemiology, University of WashingtonDepartment of Medicine, University of Washington
  • , Lawrence CoreyAffiliated withVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterDepartment of Laboratory Medicine, University of WashingtonDepartment of Medicine, University of WashingtonFred Hutchinson Cancer Research Center Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

CD8+ T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8+ T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8+ T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8+ T cell epitopes. CD8+ T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.

Keywords

HSV-2 T cells antigens/peptides/epitopes virus