CVI Accepts, published online ahead of print on 30 July 2008

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Clin. Vaccine Immunol. doi:10.1128/CVI.00123-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Gender-Dependent Human Leukocyte Antigen (HLA)-DR-Restricted Epitopes Identified from the Herpes Simplex Virus Type 1 Glycoprotein D

Xiuli Zhang, Florence A. Castelli, Xiaoming Zhu, Michele Wu, Bernard Maillère, and Lbachir BenMohamed^*

Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697-4375; CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif Sur Yvette, F-91191, France; and Center for Immunology, University of California Irvine, Irvine, CA 92697-1450, USA

^* To whom correspondence should be addressed. Email: Lbenmoha{at}uci.edu.

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 6 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 gD_49-82, gD_77-104, gD_121-152 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 (gD_49-82, gD_77-104, and gD_121-152) induced a gender, CD4+ T-cell-dependent immunity against ocular HSV-1 challenge. These results revealed a gender-dependent T cell responses to a discrete set of gD epitopes, and suggest that, while a T-cell epitope-based HSV vaccine that targets a large percent of the human population may be feasible using a limited number of immunodominant promiscuous HLA-DR-restricted epitopes; gender should be taken in account during evaluations of such vaccines.

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