title: Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes.
abstract: Cytolytic T cells play a major role in controlling herpes simplex virus type 2 (HSV-2) infections in humans. In an effort to more thoroughly evaluate the response to HSV-2 directly, ex vivo, we developed an enzyme-linked immunospot (ELISPOT) assay that utilized pools of overlapping synthetic peptides presented by autologous dendritic cells to purified CD8(+) T cells. Donor response rates to individual open reading frames (ORFs) ranged from fewer than 5% responding to as many as 70% responding, with the greatest frequency of responses (by ORF) being directed against UL39, UL25, UL27, ICP0, UL46, and UL47 in descending order of frequency. HSV-2-seropositive subjects responded to as few as 3 or as many as 46 of the 48 ORFs tested, with a median of 11 ORFs recognized. HLA-B*07 expression correlated with stronger responses overall that were directed primarily against UL49 and UL46. Cumulative precursor frequencies in the blood ranged from 500 to almost 6,000 HSV-2 spot-forming units/10(6) CD8(+) T cells. The magnitude and breadth of the response in the infected population were greater than previously appreciated. Whether this variability in the CD8(+) T-cell response within individuals is associated with the frequency of viral reactivation warrants further study.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hosken
authors.forename: Patrick
authors.initials: P
authors.lastname: McGowan
authors.forename: Amalia
authors.initials: A
authors.lastname: Meier
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.forename: Paul
authors.initials: P
authors.lastname: Sleath
authors.forename: Felecia
authors.initials: F
authors.lastname: Wagener
authors.forename: Mark
authors.initials: M
authors.lastname: Elliott
authors.forename: Ken
authors.initials: K
authors.lastname: Grabstein
authors.forename: Christine
authors.initials: C
authors.lastname: Posavad
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006558:Herpes Genitalis / Q000276:immunology* / Q000473:pathology; D006561:Herpes Simplex / Q000276:immunology / Q000503:physiopathology*; D018258:Herpesvirus 2, Human / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D016366:Open Reading Frames; D014775:Virus Activation