Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.
Identifieur interne : 002A04 ( Main/Exploration ); précédent : 002A03; suivant : 002A05Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.
Auteurs : Aziz Alami Chentoufi [États-Unis] ; Nicholas R. Binder ; Noureddine Berka ; Guillaume Durand ; Alex Nguyen ; Ilham Bettahi ; Bernard Maillère ; Lbachir BenmohamedSource :
- Journal of virology [ 1098-5514 ] ; 2008.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Antigènes HLA-DR (métabolisme), Déterminants antigéniques des lymphocytes T, Femelle, Herpès (immunologie), Humains, Interféron gamma (biosynthèse), Lymphocytes T CD4+ (immunologie), Mâle, Protéines de l'enveloppe virale (immunologie), Épitopes immunodominants.
- MESH :
- biosynthèse : Interféron gamma.
- immunologie : Herpès, Lymphocytes T CD4+, Protéines de l'enveloppe virale.
- métabolisme : Antigènes HLA-DR.
- Adolescent, Adulte, Adulte d'âge moyen, Déterminants antigéniques des lymphocytes T, Femelle, Humains, Mâle, Épitopes immunodominants.
English descriptors
- KwdEn :
- MESH :
- chemical , biosynthesis : Interferon-gamma.
- chemical , immunology : Viral Envelope Proteins.
- chemical , metabolism : HLA-DR Antigens.
- chemical : Epitopes, T-Lymphocyte, Immunodominant Epitopes.
- immunology : CD4-Positive T-Lymphocytes, Herpes Simplex.
- Adolescent, Adult, Female, Humans, Male, Middle Aged.
Abstract
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.
DOI: 10.1128/JVI.00692-08
PubMed: 18799581
Affiliations:
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Le document en format XML
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<term>Female</term>
<term>HLA-DR Antigens (metabolism)</term>
<term>Herpes Simplex (immunology)</term>
<term>Humans</term>
<term>Immunodominant Epitopes</term>
<term>Interferon-gamma (biosynthesis)</term>
<term>Male</term>
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<term>Viral Envelope Proteins (immunology)</term>
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<term>Déterminants antigéniques des lymphocytes T</term>
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<term>Humains</term>
<term>Interféron gamma (biosynthèse)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Mâle</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Épitopes immunodominants</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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<name sortKey="Binder, Nicholas R" sort="Binder, Nicholas R" uniqKey="Binder N" first="Nicholas R" last="Binder">Nicholas R. Binder</name>
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