Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.
Identifieur interne : 002079 ( PubMed/Corpus ); précédent : 002078; suivant : 002080Asymptomatic 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 Maillère ; Lbachir BenmohamedSource :
- Journal of virology [ 1098-5514 ] ; 2008.
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
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pubmed:18799581Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.</title><author><name sortKey="Chentoufi, Aziz Alami" sort="Chentoufi, Aziz Alami" uniqKey="Chentoufi A" first="Aziz Alami" last="Chentoufi">Aziz Alami Chentoufi</name><affiliation><nlm:affiliation>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California 92697-4375, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Binder, Nicholas R" sort="Binder, Nicholas R" uniqKey="Binder N" first="Nicholas R" last="Binder">Nicholas R. Binder</name></author><author><name sortKey="Berka, Noureddine" sort="Berka, Noureddine" uniqKey="Berka N" first="Noureddine" last="Berka">Noureddine Berka</name></author><author><name sortKey="Durand, Guillaume" sort="Durand, Guillaume" uniqKey="Durand G" first="Guillaume" last="Durand">Guillaume Durand</name></author><author><name sortKey="Nguyen, Alex" sort="Nguyen, Alex" uniqKey="Nguyen A" first="Alex" last="Nguyen">Alex Nguyen</name></author><author><name sortKey="Bettahi, Ilham" sort="Bettahi, Ilham" uniqKey="Bettahi I" first="Ilham" last="Bettahi">Ilham Bettahi</name></author><author><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillère">Bernard Maillère</name></author><author><name sortKey="Benmohamed, Lbachir" sort="Benmohamed, Lbachir" uniqKey="Benmohamed L" first="Lbachir" last="Benmohamed">Lbachir Benmohamed</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18799581</idno><idno type="pmid">18799581</idno><idno type="doi">10.1128/JVI.00692-08</idno><idno type="wicri:Area/PubMed/Corpus">002079</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002079</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.</title><author><name sortKey="Chentoufi, Aziz Alami" sort="Chentoufi, Aziz Alami" uniqKey="Chentoufi A" first="Aziz Alami" last="Chentoufi">Aziz Alami Chentoufi</name><affiliation><nlm:affiliation>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California 92697-4375, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Binder, Nicholas R" sort="Binder, Nicholas R" uniqKey="Binder N" first="Nicholas R" last="Binder">Nicholas R. Binder</name></author><author><name sortKey="Berka, Noureddine" sort="Berka, Noureddine" uniqKey="Berka N" first="Noureddine" last="Berka">Noureddine Berka</name></author><author><name sortKey="Durand, Guillaume" sort="Durand, Guillaume" uniqKey="Durand G" first="Guillaume" last="Durand">Guillaume Durand</name></author><author><name sortKey="Nguyen, Alex" sort="Nguyen, Alex" uniqKey="Nguyen A" first="Alex" last="Nguyen">Alex Nguyen</name></author><author><name sortKey="Bettahi, Ilham" sort="Bettahi, Ilham" uniqKey="Bettahi I" first="Ilham" last="Bettahi">Ilham Bettahi</name></author><author><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillère">Bernard Maillère</name></author><author><name sortKey="Benmohamed, Lbachir" sort="Benmohamed, Lbachir" uniqKey="Benmohamed L" first="Lbachir" last="Benmohamed">Lbachir Benmohamed</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>Epitopes, T-Lymphocyte</term><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><term>Middle Aged</term><term>Viral Envelope Proteins (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interferon-gamma</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HLA-DR Antigens</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Epitopes, T-Lymphocyte</term><term>Immunodominant Epitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Herpes Simplex</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</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(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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">18799581</PMID><DateCompleted><Year>2008</Year><Month>11</Month><Day>25</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>82</Volume><Issue>23</Issue><PubDate><Year>2008</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B.</ArticleTitle><Pagination><MedlinePgn>11792-802</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.00692-08</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chentoufi</LastName><ForeName>Aziz Alami</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California 92697-4375, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Binder</LastName><ForeName>Nicholas R</ForeName><Initials>NR</Initials></Author><Author ValidYN="Y"><LastName>Berka</LastName><ForeName>Noureddine</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Durand</LastName><ForeName>Guillaume</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Nguyen</LastName><ForeName>Alex</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Bettahi</LastName><ForeName>Ilham</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Maillère</LastName><ForeName>Bernard</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>BenMohamed</LastName><ForeName>Lbachir</ForeName><Initials>L</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>EY14900</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>EY15225</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>EY16663</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R24 EY016663</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 EY014900</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 EY015225</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2008</Year><Month>09</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018984">Epitopes, T-Lymphocyte</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006684">HLA-DR Antigens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016056">Immunodominant Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014759">Viral Envelope Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C040495">glycoprotein B, Simplexvirus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C044525">glycoprotein B, herpes simplex virus type 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>82115-62-6</RegistryNumber><NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018984" MajorTopicYN="Y">Epitopes, T-Lymphocyte</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006684" MajorTopicYN="N">HLA-DR Antigens</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006561" MajorTopicYN="N">Herpes Simplex</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016056" MajorTopicYN="N">Immunodominant Epitopes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007371" MajorTopicYN="N">Interferon-gamma</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014759" MajorTopicYN="N">Viral Envelope 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