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Journal of Virology, June 2006, p. 5509-5515, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02659-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Diversity of the CD8+ T-Cell Response to Herpes Simplex Virus Type 2 Proteins among Persons with Genital Herpes

Nancy Hosken ,6,{ddagger},{dagger} Patrick McGowan,6,§,{dagger} Amalia Meier,1,5 David M. Koelle,1,2,3,4,7 Paul Sleath,6 Felecia Wagener,6 Mark Elliott,6 Ken Grabstein,6 Christine Posavad,2 and Lawrence Corey1,2,4*

Departments of Laboratory Medicine,1 Medicine,2 Pathobiology, University of Washington, Seattle, Washington,3 Program in Infectious Diseases,4 Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, Washington,5 Corixa Corporation, Seattle Washington,6 Benaroya Research Institute, Seattle, Washington7

Received 19 December 2005/ Accepted 17 March 2006

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/106 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.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., LE-500, Seattle, WA 98109. Phone: (206) 667-6770. Fax: (206) 667-7711. E-mail: lcorey{at}u.washington.edu.

{ddagger} Present address: ZymoGenetics Corporation, Seattle, Washington.

{dagger} N.H. and P.M. contributed equally to the conception and conduct of this report.

§ Present address: Glaxo-Smithkline Biologicals Seattle, Seattle, Washington.

Journal of Virology, June 2006, p. 5509-5515, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02659-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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