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Immunodominant epitopes in herpes simplex virus type 2 glycoprotein D are recognized by CD4 lymphocytes from both HSV-1 and HSV-2 seropositive subjects.

Identifieur interne : 002977 ( Main/Exploration ); précédent : 002976; suivant : 002978

Immunodominant epitopes in herpes simplex virus type 2 glycoprotein D are recognized by CD4 lymphocytes from both HSV-1 and HSV-2 seropositive subjects.

Auteurs : Min Kim [Australie] ; Janette Taylor ; John Sidney ; Zorka Mikloska ; Neil Bodsworth ; Katerina Lagios ; Heather Dunckley ; Karen Byth-Wilson ; Martine Denis ; Robert Finlayson ; Rajiv Khanna ; Alessandro Sette ; Anthony L. Cunningham

Source :

RBID : pubmed:18941251

Descripteurs français

English descriptors

Abstract

In human recurrent cutaneous herpes simplex, there is a sequential infiltrate of CD4 and then CD8 lymphocytes into lesions. CD4 lymphocytes are the major producers of the key cytokine IFN-gamma in lesions. They recognize mainly structural proteins and especially glycoproteins D and B (gD and gB) when restimulated in vitro. Recent human vaccine trials using recombinant gD showed partial protection of HSV seronegative women against genital herpes disease and also, in placebo recipients, showed protection by prior HSV1 infection. In this study, we have defined immunodominant peptide epitopes recognized by 8 HSV1(+) and/or 16 HSV2(+) patients using (51)Cr-release cytotoxicity and IFN-gamma ELISPOT assays. Using a set of 39 overlapping 20-mer peptides, more than six immunodominant epitopes were defined in gD2 (two to six peptide epitopes were recognized for each subject). Further fine mapping of these responses for 4 of the 20-mers, using a panel of 9 internal 12-mers for each 20-mers, combined with MHC II typing and also direct in vitro binding assay of these peptides to individual DR molecules, showed more than one epitope per 20-mers and promiscuous binding of individual 20-mers and 12-mers to multiple DR types. All four 20-mer peptides were cross-recognized by both HSV1(+)/HSV2(-) and HSV1(-)/HSV2(+) subjects, but the sites of recognition differed within the 20-mers where their sequences were divergent. This work provides a basis for CD4 lymphocyte cross-recognition of gD2 and possibly cross-protection observed in previous clinical studies and in vaccine trials.

DOI: 10.4049/jimmunol.181.9.6604
PubMed: 18941251


Affiliations:


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Le document en format XML

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<keywords scheme="KwdEn" xml:lang="en">
<term>Adolescent</term>
<term>Amino Acid Sequence</term>
<term>Antigen Presentation (immunology)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>CD4-Positive T-Lymphocytes (virology)</term>
<term>Cell Line, Transformed</term>
<term>Clone Cells</term>
<term>Coculture Techniques</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>Epitopes, T-Lymphocyte (metabolism)</term>
<term>Female</term>
<term>HLA-DR Antigens (immunology)</term>
<term>HLA-DR Antigens (metabolism)</term>
<term>HLA-DRB1 Chains</term>
<term>HLA-DRB3 Chains</term>
<term>Herpes Genitalis (epidemiology)</term>
<term>Herpes Genitalis (immunology)</term>
<term>Herpes Genitalis (prevention & control)</term>
<term>Herpesvirus 1, Human (immunology)</term>
<term>Herpesvirus 1, Human (metabolism)</term>
<term>Herpesvirus 2, Human (immunology)</term>
<term>Herpesvirus 2, Human (metabolism)</term>
<term>Humans</term>
<term>Immunodominant Epitopes (immunology)</term>
<term>Immunodominant Epitopes (metabolism)</term>
<term>Molecular Sequence Data</term>
<term>Protein Binding (immunology)</term>
<term>Stomatitis, Herpetic (immunology)</term>
<term>Stomatitis, Herpetic (prevention & control)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adolescent</term>
<term>Antigènes HLA-DR (immunologie)</term>
<term>Antigènes HLA-DR (métabolisme)</term>
<term>Chaines HLA-DRB1</term>
<term>Chaines HLA-DRB3</term>
<term>Clones cellulaires</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Déterminants antigéniques des lymphocytes T (métabolisme)</term>
<term>Femelle</term>
<term>Herpès génital ()</term>
<term>Herpès génital (immunologie)</term>
<term>Herpès génital (épidémiologie)</term>
<term>Herpèsvirus humain de type 1 (immunologie)</term>
<term>Herpèsvirus humain de type 1 (métabolisme)</term>
<term>Herpèsvirus humain de type 2 (immunologie)</term>
<term>Herpèsvirus humain de type 2 (métabolisme)</term>
<term>Humains</term>
<term>Liaison aux protéines (immunologie)</term>
<term>Lignée de cellules transformées</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T CD4+ (virologie)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Présentation d'antigène (immunologie)</term>
<term>Stomatite herpétique ()</term>
<term>Stomatite herpétique (immunologie)</term>
<term>Séquence d'acides aminés</term>
<term>Techniques de coculture</term>
<term>Épitopes immunodominants (immunologie)</term>
<term>Épitopes immunodominants (métabolisme)</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Epitopes, T-Lymphocyte</term>
<term>HLA-DR Antigens</term>
<term>Immunodominant Epitopes</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en">
<term>Herpes Genitalis</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Antigènes HLA-DR</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Herpès génital</term>
<term>Herpèsvirus humain de type 1</term>
<term>Herpèsvirus humain de type 2</term>
<term>Liaison aux protéines</term>
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<term>Stomatite herpétique</term>
<term>Épitopes immunodominants</term>
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<term>Herpes Genitalis</term>
<term>Herpesvirus 1, Human</term>
<term>Herpesvirus 2, Human</term>
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<term>CD4-Positive T-Lymphocytes</term>
<term>Epitopes, T-Lymphocyte</term>
<term>HLA-DR Antigens</term>
<term>Herpesvirus 1, Human</term>
<term>Herpesvirus 2, Human</term>
<term>Immunodominant Epitopes</term>
<term>Viral Envelope Proteins</term>
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<term>Déterminants antigéniques des lymphocytes T</term>
<term>Herpèsvirus humain de type 1</term>
<term>Herpèsvirus humain de type 2</term>
<term>Lymphocytes T CD4+</term>
<term>Protéines de l'enveloppe virale</term>
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<term>Lymphocytes T CD4+</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>CD4-Positive T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr">
<term>Herpès génital</term>
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<term>Adolescent</term>
<term>Amino Acid Sequence</term>
<term>Cell Line, Transformed</term>
<term>Clone Cells</term>
<term>Coculture Techniques</term>
<term>Female</term>
<term>HLA-DRB1 Chains</term>
<term>HLA-DRB3 Chains</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adolescent</term>
<term>Chaines HLA-DRB1</term>
<term>Chaines HLA-DRB3</term>
<term>Clones cellulaires</term>
<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Herpès génital</term>
<term>Humains</term>
<term>Lignée de cellules transformées</term>
<term>Stomatite herpétique</term>
<term>Séquence d'acides aminés</term>
<term>Techniques de coculture</term>
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<front>
<div type="abstract" xml:lang="en">In human recurrent cutaneous herpes simplex, there is a sequential infiltrate of CD4 and then CD8 lymphocytes into lesions. CD4 lymphocytes are the major producers of the key cytokine IFN-gamma in lesions. They recognize mainly structural proteins and especially glycoproteins D and B (gD and gB) when restimulated in vitro. Recent human vaccine trials using recombinant gD showed partial protection of HSV seronegative women against genital herpes disease and also, in placebo recipients, showed protection by prior HSV1 infection. In this study, we have defined immunodominant peptide epitopes recognized by 8 HSV1(+) and/or 16 HSV2(+) patients using (51)Cr-release cytotoxicity and IFN-gamma ELISPOT assays. Using a set of 39 overlapping 20-mer peptides, more than six immunodominant epitopes were defined in gD2 (two to six peptide epitopes were recognized for each subject). Further fine mapping of these responses for 4 of the 20-mers, using a panel of 9 internal 12-mers for each 20-mers, combined with MHC II typing and also direct in vitro binding assay of these peptides to individual DR molecules, showed more than one epitope per 20-mers and promiscuous binding of individual 20-mers and 12-mers to multiple DR types. All four 20-mer peptides were cross-recognized by both HSV1(+)/HSV2(-) and HSV1(-)/HSV2(+) subjects, but the sites of recognition differed within the 20-mers where their sequences were divergent. This work provides a basis for CD4 lymphocyte cross-recognition of gD2 and possibly cross-protection observed in previous clinical studies and in vaccine trials.</div>
</front>
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