Gender-dependent HLA-DR-restricted epitopes identified from herpes simplex virus type 1 glycoprotein D.
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 gD(49-82), gD(77-104), and 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- 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.
Zhang
Xiuli
X
Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine School of Medicine, Irvine, California 92697-4375, USA.
Castelli
Florence A
FA
Zhu
Xiaoming
X
Wu
Michele
M
Maillère
Bernard
B
BenMohamed
Lbachir
L
D000293:Adolescent; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D012723:Sex; D014759:Viral Envelope Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D022283:Herpesvirus Vaccines; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C069093:herpes simplex virus-1 glycoprotein D vaccine