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Clinical and Vaccine Immunology, September 2008, p. 1436-1449, Vol. 15, No. 9
1071-412X/08/$08.00+0     doi:10.1128/CVI.00123-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Gender-Dependent HLA-DR-Restricted Epitopes Identified from Herpes Simplex Virus Type 1 Glycoprotein D{triangledown}

Xiuli Zhang,1 Florence A. Castelli,2 Xiaoming Zhu,1 Michele Wu,1 Bernard Maillère,2 and Lbachir BenMohamed1,3*

Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine School of Medicine, Irvine, California 92697-4375,1 CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif Sur Yvette F-91191, France,2 Center for Immunology, University of California Irvine, Irvine, California 92697-14503

Received 6 April 2008/ Returned for modification 29 May 2008/ Accepted 18 July 2008

In recent clinical trials, a herpes simplex virus (HSV) recombinant glycoprotein D (gD) vaccine was more efficacious in woman than in men. Here we report six HLA-DR-restricted T-cell gD epitope peptides that bind to multiple HLA-DR (DR1, DR4, DR7, DR13, DR15, and DRB5) molecules that represent a large proportion of the human population. Four of these peptides recalled naturally primed CD4+ T cells in up to 45% of the 46 HSV-seropositive, asymptomatic individuals studied. For the gD49-82, gD77-104, and gD121-152 peptides, the CD4+ T-cell responses detected in HSV-seropositive, asymptomatic women were higher and more frequent than the responses detected in men. Immunization of susceptible DRB1*0101 transgenic mice with a mixture of three newly identified, gender-dependent, immunodominant epitope peptides (gD49-82, gD77-104, and gD121-152) induced a gender- and CD4+ T-cell-dependent immunity against ocular HSV type 1 challenge. These results revealed a gender-dependent T-cell response to a discrete set of gD epitopes and suggest that while a T-cell epitope-based HSV vaccine that targets a large percentage of the human population may be feasible with a limited number of immunodominant promiscuous HLA-DR-restricted epitopes, gender should be taken into account during evaluations of such 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 30 July 2008.

Clinical and Vaccine Immunology, September 2008, p. 1436-1449, Vol. 15, No. 9
1071-412X/08/$08.00+0     doi:10.1128/CVI.00123-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zandian, M., Belisle, R., Mott, K. R., Nusinowitz, S., Hofman, F. M., Ghiasi, H. (2009). Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2. IOVS 50: 3275-3282 [Abstract] [Full Text]  
  • Chentoufi, A. A., Binder, N. R., Berka, N., Durand, G., Nguyen, A., Bettahi, I., Maillere, B., BenMohamed, L. (2008). Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B. J. Virol. 82: 11792-11802 [Abstract] [Full Text]  


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