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Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B

Identifieur interne : 000069 ( PascalFrancis/Corpus ); précédent : 000068; suivant : 000070

Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B

Auteurs : Aziz Alami Chentoufi ; Nicholas R. Binder ; Noureddine Berka ; Guillaume Durand ; Alex Nguyen ; Ilham Bettahi ; Bernard Maillere ; Lbachir Benmohamed

Source :

RBID : Pascal:09-0013229

Descripteurs français

English descriptors

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 gB161-175 and gB166-180 within G4 and gB661-675 within G14 recalled the strongest HLA-DR-dependent CD4+ T-cell proliferation and gamma interferon production. gB166-180, gB661-675, and gB666-680 elicited ex vivo CD4+ cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB166-180 and gB666-680 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 gB661-675 (P < 0.0001). Thus, we identified three previously unrecognized CD4+ CTL peptide epitopes in HSV-1 gB. Among these, gB166-180 and gB666-680 appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

pA  
A01 01  1    @0 0022-538X
A03   1    @0 J. virol.
A05       @2 82
A06       @2 23
A08 01  1  ENG  @1 Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B
A11 01  1    @1 ALAMI CHENTOUFI (Aziz)
A11 02  1    @1 BINDER (Nicholas R.)
A11 03  1    @1 BERKA (Noureddine)
A11 04  1    @1 DURAND (Guillaume)
A11 05  1    @1 NGUYEN (Alex)
A11 06  1    @1 BETTAHI (Ilham)
A11 07  1    @1 MAILLERE (Bernard)
A11 08  1    @1 BENMOHAMED (Lbachir)
A14 01      @1 Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine @2 Irvine, California 92697-4375 @3 USA @Z 1 aut. @Z 2 aut. @Z 5 aut. @Z 6 aut. @Z 8 aut.
A14 02      @1 Tissue Typing Laboratory @2 Calgary, Alberta T2L2K8 @3 CAN @Z 3 aut.
A14 03      @1 CEA, iBiTecS, Service d'Ingenierie Moléculaire des Protéines (SIMOPRO) @2 Gif Sur Yvette 91191 @3 FRA @Z 4 aut. @Z 7 aut.
A14 04      @1 Center for Immunology, University of California Irvine @2 Irvine, California 92697-1450 @3 USA @Z 8 aut.
A20       @1 11792-11802
A21       @1 2008
A23 01      @0 ENG
A43 01      @1 INIST @2 13592 @5 354000184531680310
A44       @0 0000 @1 © 2009 INIST-CNRS. All rights reserved.
A45       @0 80 ref.
A47 01  1    @0 09-0013229
A60       @1 P
A61       @0 A
A64 01  1    @0 Journal of virology
A66 01      @0 USA
C01 01    ENG  @0 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 gB161-175 and gB166-180 within G4 and gB661-675 within G14 recalled the strongest HLA-DR-dependent CD4+ T-cell proliferation and gamma interferon production. gB166-180, gB661-675, and gB666-680 elicited ex vivo CD4+ cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB166-180 and gB666-680 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 gB661-675 (P < 0.0001). Thus, we identified three previously unrecognized CD4+ CTL peptide epitopes in HSV-1 gB. Among these, gB166-180 and gB666-680 appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.
C02 01  X    @0 002A05C10
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C03 01  X  ENG  @0 Human @5 01
C03 01  X  SPA  @0 Hombre @5 01
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C03 02  X  SPA  @0 Herpesvirus hominis @2 NW @5 02
C03 03  X  FRE  @0 Asymptomatique @5 05
C03 03  X  ENG  @0 Asymptomatic @5 05
C03 03  X  SPA  @0 Asintomático @5 05
C03 04  X  FRE  @0 Lymphocyte T @5 06
C03 04  X  ENG  @0 T-Lymphocyte @5 06
C03 04  X  SPA  @0 Linfocito T @5 06
C03 05  X  FRE  @0 Lymphocyte T cytotoxique @5 07
C03 05  X  ENG  @0 Cytotoxic T lymphocyte @5 07
C03 05  X  SPA  @0 Linfocito T citotóxico @5 07
C03 06  X  FRE  @0 Déterminant antigénique @5 08
C03 06  X  ENG  @0 Antigenic determinant @5 08
C03 06  X  SPA  @0 Determinante antigénico @5 08
C03 07  X  FRE  @0 Glycoprotéine @5 09
C03 07  X  ENG  @0 Glycoprotein @5 09
C03 07  X  SPA  @0 Glicoproteína @5 09
C03 08  X  FRE  @0 Virologie @5 10
C03 08  X  ENG  @0 Virology @5 10
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C03 09  X  FRE  @0 Antigène CD4 @4 INC @5 79
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Format Inist (serveur)

NO : PASCAL 09-0013229 INIST
ET : Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B
AU : ALAMI CHENTOUFI (Aziz); BINDER (Nicholas R.); BERKA (Noureddine); DURAND (Guillaume); NGUYEN (Alex); BETTAHI (Ilham); MAILLERE (Bernard); BENMOHAMED (Lbachir)
AF : Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine/Irvine, California 92697-4375/Etats-Unis (1 aut., 2 aut., 5 aut., 6 aut., 8 aut.); Tissue Typing Laboratory/Calgary, Alberta T2L2K8/Canada (3 aut.); CEA, iBiTecS, Service d'Ingenierie Moléculaire des Protéines (SIMOPRO)/Gif Sur Yvette 91191/France (4 aut., 7 aut.); Center for Immunology, University of California Irvine/Irvine, California 92697-1450/Etats-Unis (8 aut.)
DT : Publication en série; Niveau analytique
SO : Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2008; Vol. 82; No. 23; Pp. 11792-11802; Bibl. 80 ref.
LA : Anglais
EA : 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 gB161-175 and gB166-180 within G4 and gB661-675 within G14 recalled the strongest HLA-DR-dependent CD4+ T-cell proliferation and gamma interferon production. gB166-180, gB661-675, and gB666-680 elicited ex vivo CD4+ cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB166-180 and gB666-680 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 gB661-675 (P < 0.0001). Thus, we identified three previously unrecognized CD4+ CTL peptide epitopes in HSV-1 gB. Among these, gB166-180 and gB666-680 appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.
CC : 002A05C10
FD : Homme; Herpesvirus hominis; Asymptomatique; Lymphocyte T; Lymphocyte T cytotoxique; Déterminant antigénique; Glycoprotéine; Virologie; Antigène CD4
FG : Alphaherpesvirinae; Herpesviridae; Virus
ED : Human; Herpesvirus hominis; Asymptomatic; T-Lymphocyte; Cytotoxic T lymphocyte; Antigenic determinant; Glycoprotein; Virology
EG : Alphaherpesvirinae; Herpesviridae; Virus
SD : Hombre; Herpesvirus hominis; Asintomático; Linfocito T; Linfocito T citotóxico; Determinante antigénico; Glicoproteína; Virología
LO : INIST-13592.354000184531680310
ID : 09-0013229

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Pascal:09-0013229

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<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
<sub>161-175</sub>
and gB
<sub>166-180</sub>
within G4 and gB
<sub>661-675</sub>
within G14 recalled the strongest HLA-DR-dependent CD4
<sup>+</sup>
T-cell proliferation and gamma interferon production. gB
<sub>166-180,</sub>
gB
<sub>661-675</sub>
, and gB
<sub>666-680</sub>
elicited ex vivo CD4
<sup>+</sup>
cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB
<sub>166-180</sub>
and gB
<sub>666-680</sub>
peptide epitopes were strongly recognized by CD4
<sup>+</sup>
T cells from 10 of 10 asymptomatic patients but not by CD4
<sup>+</sup>
T cells from 10 of 10 symptomatic patients (P < 0.0001; analysis of variance posttest). Inversely, CD4
<sup>+</sup>
T cells from symptomatic patients preferentially recognized gB
<sub>661-675</sub>
(P < 0.0001). Thus, we identified three previously unrecognized CD4
<sup>+</sup>
CTL peptide epitopes in HSV-1 gB. Among these, gB
<sub>166-180</sub>
and gB
<sub>666-680</sub>
appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.</div>
</front>
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<sub>161-175</sub>
and gB
<sub>166-180</sub>
within G4 and gB
<sub>661-675</sub>
within G14 recalled the strongest HLA-DR-dependent CD4
<sup>+</sup>
T-cell proliferation and gamma interferon production. gB
<sub>166-180,</sub>
gB
<sub>661-675</sub>
, and gB
<sub>666-680</sub>
elicited ex vivo CD4
<sup>+</sup>
cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB
<sub>166-180</sub>
and gB
<sub>666-680</sub>
peptide epitopes were strongly recognized by CD4
<sup>+</sup>
T cells from 10 of 10 asymptomatic patients but not by CD4
<sup>+</sup>
T cells from 10 of 10 symptomatic patients (P < 0.0001; analysis of variance posttest). Inversely, CD4
<sup>+</sup>
T cells from symptomatic patients preferentially recognized gB
<sub>661-675</sub>
(P < 0.0001). Thus, we identified three previously unrecognized CD4
<sup>+</sup>
CTL peptide epitopes in HSV-1 gB. Among these, gB
<sub>166-180</sub>
and gB
<sub>666-680</sub>
appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.</s0>
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<NO>PASCAL 09-0013229 INIST</NO>
<ET>Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B</ET>
<AU>ALAMI CHENTOUFI (Aziz); BINDER (Nicholas R.); BERKA (Noureddine); DURAND (Guillaume); NGUYEN (Alex); BETTAHI (Ilham); MAILLERE (Bernard); BENMOHAMED (Lbachir)</AU>
<AF>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine/Irvine, California 92697-4375/Etats-Unis (1 aut., 2 aut., 5 aut., 6 aut., 8 aut.); Tissue Typing Laboratory/Calgary, Alberta T2L2K8/Canada (3 aut.); CEA, iBiTecS, Service d'Ingenierie Moléculaire des Protéines (SIMOPRO)/Gif Sur Yvette 91191/France (4 aut., 7 aut.); Center for Immunology, University of California Irvine/Irvine, California 92697-1450/Etats-Unis (8 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2008; Vol. 82; No. 23; Pp. 11792-11802; Bibl. 80 ref.</SO>
<LA>Anglais</LA>
<EA>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
<sub>161-175</sub>
and gB
<sub>166-180</sub>
within G4 and gB
<sub>661-675</sub>
within G14 recalled the strongest HLA-DR-dependent CD4
<sup>+</sup>
T-cell proliferation and gamma interferon production. gB
<sub>166-180,</sub>
gB
<sub>661-675</sub>
, and gB
<sub>666-680</sub>
elicited ex vivo CD4
<sup>+</sup>
cytotoxic T cells (CTLs) that lysed autologous HSV-1- and vaccinia virus (expressing gB)-infected lymphoblastoid cell lines. Interestingly, gB
<sub>166-180</sub>
and gB
<sub>666-680</sub>
peptide epitopes were strongly recognized by CD4
<sup>+</sup>
T cells from 10 of 10 asymptomatic patients but not by CD4
<sup>+</sup>
T cells from 10 of 10 symptomatic patients (P < 0.0001; analysis of variance posttest). Inversely, CD4
<sup>+</sup>
T cells from symptomatic patients preferentially recognized gB
<sub>661-675</sub>
(P < 0.0001). Thus, we identified three previously unrecognized CD4
<sup>+</sup>
CTL peptide epitopes in HSV-1 gB. Among these, gB
<sub>166-180</sub>
and gB
<sub>666-680</sub>
appear to be "asymptomatic" peptide epitopes and therefore should be considered in the design of future herpes vaccines.</EA>
<CC>002A05C10</CC>
<FD>Homme; Herpesvirus hominis; Asymptomatique; Lymphocyte T; Lymphocyte T cytotoxique; Déterminant antigénique; Glycoprotéine; Virologie; Antigène CD4</FD>
<FG>Alphaherpesvirinae; Herpesviridae; Virus</FG>
<ED>Human; Herpesvirus hominis; Asymptomatic; T-Lymphocyte; Cytotoxic T lymphocyte; Antigenic determinant; Glycoprotein; Virology</ED>
<EG>Alphaherpesvirinae; Herpesviridae; Virus</EG>
<SD>Hombre; Herpesvirus hominis; Asintomático; Linfocito T; Linfocito T citotóxico; Determinante antigénico; Glicoproteína; Virología</SD>
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