Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.
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 gB(161-175) and gB(166-180) within G4 and gB(661-675) within G14 recalled the strongest HLA-DR-dependent CD4(+) T-cell proliferation and gamma interferon production. gB(166-180), gB(661-675), and gB(666-680) elicited ex vivo CD4(+) cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB(166-180) and gB(666-680) 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 gB(661-675) (P < 0.0001). Thus, we identified three previously unrecognized CD4(+) CTL peptide epitopes in HSV-1 gB. Among these, gB(166-180) and gB(666-680) appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.
Chentoufi
Aziz Alami
AA
Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California 92697-4375, USA.
Binder
Nicholas R
NR
Berka
Noureddine
N
Durand
Guillaume
G
Nguyen
Alex
A
Bettahi
Ilham
I
Maillère
Bernard
B
BenMohamed
Lbachir
L
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D014759:Viral Envelope Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C044525:glycoprotein B, herpes simplex virus type 2; D007371:Interferon-gamma
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