Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B
Identifieur interne : 000181 ( France/Analysis ); précédent : 000180; suivant : 000182Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B
Auteurs : Aziz Alami Chentoufi [États-Unis] ; Nicholas R. Binder [États-Unis] ; Noureddine Berka [Canada] ; Guillaume Durand [France] ; Alex Nguyen [États-Unis] ; Ilham Bettahi [États-Unis] ; Bernard Maillere [France] ; Lbachir Benmohamed [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2008.
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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.
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Herbert Eye Institute, University of California Irvine, School of Medicine</s1><s2>Irvine, California 92697-4375</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine, California 92697-4375</wicri:noRegion></affiliation></author><author><name sortKey="Binder, Nicholas R" sort="Binder, Nicholas R" uniqKey="Binder N" first="Nicholas R." last="Binder">Nicholas R. Binder</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine</s1><s2>Irvine, California 92697-4375</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine, California 92697-4375</wicri:noRegion></affiliation></author><author><name sortKey="Berka, Noureddine" sort="Berka, Noureddine" uniqKey="Berka N" first="Noureddine" last="Berka">Noureddine Berka</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Tissue Typing Laboratory</s1><s2>Calgary, Alberta T2L2K8</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Tissue Typing Laboratory</wicri:noRegion></affiliation></author><author><name sortKey="Durand, Guillaume" sort="Durand, Guillaume" uniqKey="Durand G" first="Guillaume" last="Durand">Guillaume Durand</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>CEA, iBiTecS, Service d'Ingenierie Moléculaire des Protéines (SIMOPRO)</s1><s2>Gif Sur Yvette 91191</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Nguyen, Alex" sort="Nguyen, Alex" uniqKey="Nguyen A" first="Alex" last="Nguyen">Alex Nguyen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine</s1><s2>Irvine, California 92697-4375</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine, California 92697-4375</wicri:noRegion></affiliation></author><author><name sortKey="Bettahi, Ilham" sort="Bettahi, Ilham" uniqKey="Bettahi I" first="Ilham" last="Bettahi">Ilham Bettahi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine</s1><s2>Irvine, California 92697-4375</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine, California 92697-4375</wicri:noRegion></affiliation></author><author><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillere">Bernard Maillere</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>CEA, iBiTecS, Service d'Ingenierie Moléculaire des Protéines (SIMOPRO)</s1><s2>Gif Sur Yvette 91191</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Benmohamed, Lbachir" sort="Benmohamed, Lbachir" uniqKey="Benmohamed L" first="Lbachir" last="Benmohamed">Lbachir Benmohamed</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine</s1><s2>Irvine, California 92697-4375</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine, California 92697-4375</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Center for Immunology, University of California Irvine</s1><s2>Irvine, California 92697-1450</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine, California 92697-1450</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigenic determinant</term><term>Asymptomatic</term><term>Cytotoxic T lymphocyte</term><term>Glycoprotein</term><term>Herpesvirus hominis</term><term>Human</term><term>T-Lymphocyte</term><term>Virology</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Homme</term><term>Herpesvirus hominis</term><term>Asymptomatique</term><term>Lymphocyte T</term><term>Lymphocyte T cytotoxique</term><term>Déterminant antigénique</term><term>Glycoprotéine</term><term>Virologie</term><term>Antigène CD4</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><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<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></TEI><affiliations><list><country><li>Canada</li><li>France</li><li>États-Unis</li></country><region><li>Île-de-France</li></region></list><tree><country name="États-Unis"><noRegion><name sortKey="Alami Chentoufi, Aziz" sort="Alami Chentoufi, Aziz" uniqKey="Alami Chentoufi A" first="Aziz" last="Alami Chentoufi">Aziz Alami Chentoufi</name></noRegion><name sortKey="Benmohamed, Lbachir" sort="Benmohamed, Lbachir" uniqKey="Benmohamed L" first="Lbachir" last="Benmohamed">Lbachir Benmohamed</name><name sortKey="Benmohamed, Lbachir" sort="Benmohamed, Lbachir" uniqKey="Benmohamed L" first="Lbachir" last="Benmohamed">Lbachir Benmohamed</name><name sortKey="Bettahi, Ilham" sort="Bettahi, Ilham" uniqKey="Bettahi I" first="Ilham" last="Bettahi">Ilham Bettahi</name><name sortKey="Binder, Nicholas R" sort="Binder, Nicholas R" uniqKey="Binder N" first="Nicholas R." last="Binder">Nicholas R. Binder</name><name sortKey="Nguyen, Alex" sort="Nguyen, Alex" uniqKey="Nguyen A" first="Alex" last="Nguyen">Alex Nguyen</name></country><country name="Canada"><noRegion><name sortKey="Berka, Noureddine" sort="Berka, Noureddine" uniqKey="Berka N" first="Noureddine" last="Berka">Noureddine Berka</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Durand, Guillaume" sort="Durand, Guillaume" uniqKey="Durand G" first="Guillaume" last="Durand">Guillaume Durand</name></region><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillere">Bernard Maillere</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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