title: Diversity in CD8(+) T cell function and epitope breadth among persons with genital herpes.
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.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Laing
authors.forename: Amalia S
authors.initials: AS
authors.lastname: Magaret
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Mueller
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D000328:Adult; D000368:Aged; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015550:Cell Degranulation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006558:Herpes Genitalis / Q000175:diagnosis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte