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Journal of Virology, December 2008, p. 11792-11802, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.00692-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B{triangledown}

Aziz Alami Chentoufi,1 Nicholas R. Binder,1 Noureddine Berka,2 Guillaume Durand,3 Alex Nguyen,1 Ilham Bettahi,1 Bernard Maillère,3 and Lbachir BenMohamed1,4*

Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California 92697-4375,1 Tissue Typing Laboratory, Calgary, Alberta T2L2K8, Canada,2 CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif Sur Yvette F-91191, France,3 Center for Immunology, University of California Irvine, Irvine, California 92697-14504

Received 28 March 2008/ Accepted 2 September 2008

The identification of "asymptomatic" (i.e., protective) epitopes recognized by T cells from herpes simplex virus (HSV)-seropositive healthy individuals is a prerequisite for an effective vaccine. Using the PepScan epitope mapping strategy, a library of 179 potential peptide epitopes (15-mers overlapping by 10 amino acids) was identified from HSV type 1 (HSV-1) glycoprotein B (gB), an antigen that induces protective immunity in both animal models and humans. Eighteen groups (G1 to G18) of 10 adjacent peptides each were first screened for T-cell antigenicity in 38 HSV-1-seropositive but HSV-2-seronegative individuals. Individual peptides within the two immunodominant groups (i.e., G4 and G14) were further screened with T cells from HLA-DR-genotyped and clinically defined symptomatic (n = 10) and asymptomatic (n = 10) HSV-1-seropositive healthy individuals. Peptides gB161-175 and gB166-180 within G4 and gB661-675 within G14 recalled the strongest HLA-DR-dependent CD4+ T-cell proliferation and gamma interferon production. gB166-180, gB661-675, and gB666-680 elicited ex vivo CD4+ cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB166-180 and gB666-680 peptide epitopes were strongly recognized by CD4+ T cells from 10 of 10 asymptomatic patients but not by CD4+ T cells from 10 of 10 symptomatic patients (P < 0.0001; analysis of variance posttest). Inversely, CD4+ T cells from symptomatic patients preferentially recognized gB661-675 (P < 0.0001). Thus, we identified three previously unrecognized CD4+ CTL peptide epitopes in HSV-1 gB. Among these, gB166-180 and gB666-680 appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.

* Corresponding author. Mailing address: Laboratory of Cellular and Molecular Immunology, University of California Irvine Medical Center, 101 The City Drive, Bldg. 55, Room 202, Orange, CA 92868. Phone: (714) 456-7371. Fax: (714) 456-5073. E-mail: Lbenmoha{at}uci.edu

{triangledown} Published ahead of print on 17 September 2008.

Journal of Virology, December 2008, p. 11792-11802, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.00692-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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