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

Authors

  • Kerry J. Laing
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
  • Amalia S. Magaret
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
    • Department of Laboratory MedicineUniversity of Washington
  • Dawn E. Mueller
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
  • Lin Zhao
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
  • Christine Johnston
    • Department of Laboratory MedicineUniversity of Washington
  • Stephen C. De Rosa
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
    • HIV Vaccine Trials NetworkFred Hutchinson Cancer Research Center
    • Department of Laboratory MedicineUniversity of Washington
    • Center for AIDS ResearchUniversity of Washington
  • David M. Koelle
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
    • Department of Laboratory MedicineUniversity of Washington
    • Department of MedicineUniversity of Washington
    • Department of Global HealthUniversity of Washington
    • Benaroya Research Institute
  • Anna Wald
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
    • Department of Laboratory MedicineUniversity of Washington
    • Department of EpidemiologyUniversity of Washington
    • Department of MedicineUniversity of Washington
    • Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research Center
    • Department of Laboratory MedicineUniversity of Washington
    • Department of MedicineUniversity of Washington
    • Fred Hutchinson Cancer Research Center
Article

DOI: 10.1007/s10875-010-9441-2

Cite this article as:
Laing, K.J., Magaret, A.S., Mueller, D.E. et al. J Clin Immunol (2010) 30: 703. doi:10.1007/s10875-010-9441-2

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 S1 Cytokine 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 S2 HLA-A and -B types represented in seropositive subjects (DOCX 15 kb)

Copyright information

© Springer Science+Business Media, LLC 2010