Journal of Clinical Immunology

, Volume 30, Issue 5, pp 703–722 | Cite as

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

  • Kerry J. Laing
  • Amalia S. Magaret
  • Dawn E. Mueller
  • Lin Zhao
  • Christine Johnston
  • Stephen C. De Rosa
  • David M. Koelle
  • Anna Wald
  • Lawrence Corey
Article

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 

Abbreviations

ICS

Intracellular cytokine staining

ORF

Open-reading frame

CEF

CMV, EBV and flu

MFI

Median fluorescence intensity

Supplementary material

10875_2010_9441_MOESM1_ESM.docx (15 kb)
Supplementary Table S1Cytokine responses of HSV-2-specific CD8+ T cells by open-reading frame (percent responders) (DOCX 15 kb)
10875_2010_9441_MOESM2_ESM.docx (16 kb)
Supplementary Table S2HLA-A and -B types represented in seropositive subjects (DOCX 15 kb)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kerry J. Laing
    • 1
  • Amalia S. Magaret
    • 1
    • 3
  • Dawn E. Mueller
    • 1
  • Lin Zhao
    • 1
  • Christine Johnston
    • 3
  • Stephen C. De Rosa
    • 1
    • 2
    • 3
    • 6
  • David M. Koelle
    • 1
    • 3
    • 5
    • 7
    • 8
  • Anna Wald
    • 1
    • 3
    • 4
    • 5
  • Lawrence Corey
    • 1
    • 3
    • 5
    • 9
  1. 1.Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.HIV Vaccine Trials NetworkFred Hutchinson Cancer Research CenterSeattleUSA
  3. 3.Department of Laboratory MedicineUniversity of WashingtonSeattleUSA
  4. 4.Department of EpidemiologyUniversity of WashingtonSeattleUSA
  5. 5.Department of MedicineUniversity of WashingtonSeattleUSA
  6. 6.Center for AIDS ResearchUniversity of WashingtonSeattleUSA
  7. 7.Department of Global HealthUniversity of WashingtonSeattleUSA
  8. 8.Benaroya Research InstituteSeattleUSA
  9. 9.Fred Hutchinson Cancer Research CenterSeattleUSA

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