Increased Breadth and Depth of Cytotoxic T Lymphocytes Responses against HIV-1-B Nef by Inclusion of Epitope Variant Sequences
Identifieur interne : 002456 ( Main/Exploration ); précédent : 002455; suivant : 002457Increased Breadth and Depth of Cytotoxic T Lymphocytes Responses against HIV-1-B Nef by Inclusion of Epitope Variant Sequences
Auteurs : Morgane Rolland [États-Unis] ; Nicole Frahm [États-Unis] ; David C. Nickle [États-Unis] ; Nebojsa Jojic [Espagne] ; Wenjie Deng [États-Unis] ; Todd M. Allen [États-Unis] ; Christian Brander [États-Unis, Espagne] ; David E. Heckerman [États-Unis] ; James I. Mullins [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Descripteurs français
- KwdFr :
- Humains, Interféron gamma (immunologie), Lymphocytes T cytotoxiques (immunologie), Mutation (génétique), Peptides (), Peptides (immunologie), Produits du gène nef du virus de l'immunodéficience humaine (immunologie), Réactions croisées (immunologie), Séquence consensus, Séquence d'acides aminés, Séquence nucléotidique, Test ELISpot, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie), Épitopes (immunologie).
- MESH :
- génétique : Mutation.
- immunologie : Interféron gamma, Lymphocytes T cytotoxiques, Peptides, Produits du gène nef du virus de l'immunodéficience humaine, Réactions croisées, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Épitopes.
- Humains, Peptides, Séquence consensus, Séquence d'acides aminés, Séquence nucléotidique, Test ELISpot.
English descriptors
- KwdEn :
- Amino Acid Sequence, Base Sequence, Consensus Sequence, Cross Reactions (immunology), Enzyme-Linked Immunospot Assay, Epitopes (immunology), HIV-1 (immunology), Humans, Interferon-gamma (immunology), Mutation (genetics), Peptides (chemistry), Peptides (immunology), T-Lymphocytes, Cytotoxic (immunology), nef Gene Products, Human Immunodeficiency Virus (immunology).
- MESH :
- chemical , chemistry : Peptides.
- chemical , immunology : Epitopes, Interferon-gamma, Peptides, nef Gene Products, Human Immunodeficiency Virus.
- genetics : Mutation.
- immunology : Cross Reactions, HIV-1, T-Lymphocytes, Cytotoxic.
- Amino Acid Sequence, Base Sequence, Consensus Sequence, Enzyme-Linked Immunospot Assay, Humans.
Abstract
Different vaccine approaches cope with HIV-1 diversity, ranging from centralized1–4 to variability-encompassing5–7antigens. For all these strategies, a concern remains: how does HIV-1 diversity impact epitope recognition by the immune system? We studied the relationship between HIV-1 diversity and CD8+ T Lymphocytes (CTL) targeting of HIV-1 subtype B Nef using 944 peptides (10-mers overlapping by nine amino acids (AA)) that corresponded to consensus peptides and their most common variants in the HIV-1-B virus population. IFN-γ ELISpot assays were performed using freshly isolated PBMC from 26 HIV-1-infected persons. Three hundred and fifty peptides elicited a response in at least one individual. Individuals targeted a median of 7 discrete regions. Overall, 33% of responses were directed against viral variants but not elicited against consensus-based test peptides. However, there was no significant relationship between the frequency of a 10-mer in the viral population and either its frequency of recognition (Spearman's correlation coefficient ρ = 0.24) or the magnitude of the responses (ρ = 0.16). We found that peptides with a single mutation compared to the consensus were likely to be recognized (especially if the change was conservative) and to elicit responses of similar magnitude as the consensus peptide. Our results indicate that cross-reactivity between rare and frequent variants is likely to play a role in the expansion of CTL responses, and that maximizing antigenic diversity in a vaccine may increase the breadth and depth of CTL responses. However, since there are few obvious preferred pathways to virologic escape, the diversity that may be required to block all potential escape pathways may be too large for a realistic vaccine to accommodate. Furthermore, since peptides were not recognized based on their frequency in the population, it remains unclear by which mechanisms variability-inclusive antigens (i.e., constructs enriched with frequent variants) expand CTL recognition.
Url:
DOI: 10.1371/journal.pone.0017969
PubMed: 21464919
PubMed Central: 3065451
Affiliations:
- Espagne, États-Unis
- Catalogne, Massachusetts, Washington (État)
- Barcelone, Seattle
- Université de Washington
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Base Sequence</term>
<term>Consensus Sequence</term>
<term>Cross Reactions (immunology)</term>
<term>Enzyme-Linked Immunospot Assay</term>
<term>Epitopes (immunology)</term>
<term>HIV-1 (immunology)</term>
<term>Humans</term>
<term>Interferon-gamma (immunology)</term>
<term>Mutation (genetics)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (immunology)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
<term>nef Gene Products, Human Immunodeficiency Virus (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Humains</term>
<term>Interféron gamma (immunologie)</term>
<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Mutation (génétique)</term>
<term>Peptides ()</term>
<term>Peptides (immunologie)</term>
<term>Produits du gène nef du virus de l'immunodéficience humaine (immunologie)</term>
<term>Réactions croisées (immunologie)</term>
<term>Séquence consensus</term>
<term>Séquence d'acides aminés</term>
<term>Séquence nucléotidique</term>
<term>Test ELISpot</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term>
<term>Épitopes (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Peptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes</term>
<term>Interferon-gamma</term>
<term>Peptides</term>
<term>nef Gene Products, Human Immunodeficiency Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Mutation</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Interféron gamma</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Peptides</term>
<term>Produits du gène nef du virus de l'immunodéficience humaine</term>
<term>Réactions croisées</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cross Reactions</term>
<term>HIV-1</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Base Sequence</term>
<term>Consensus Sequence</term>
<term>Enzyme-Linked Immunospot Assay</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Peptides</term>
<term>Séquence consensus</term>
<term>Séquence d'acides aminés</term>
<term>Séquence nucléotidique</term>
<term>Test ELISpot</term>
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<front><div type="abstract" xml:lang="en"><p>Different vaccine approaches cope with HIV-1
diversity, ranging from
centralized<sup>1–4</sup>
to
variability-encompassing<sup>5–7</sup>
antigens. For all these strategies, a concern
remains: how does HIV-1 diversity impact epitope
recognition by the immune system? We studied the
relationship between HIV-1 diversity and
CD8<sup>+</sup>
T Lymphocytes (CTL) targeting
of HIV-1 subtype B Nef using 944 peptides (10-mers
overlapping by nine amino acids (AA)) that
corresponded to consensus peptides and their most
common variants in the HIV-1-B virus population.
IFN-γ ELISpot assays were performed using
freshly isolated PBMC from 26 HIV-1-infected
persons. Three hundred and fifty peptides elicited
a response in at least one individual. Individuals
targeted a median of 7 discrete regions. Overall,
33% of responses were directed against
viral variants but not elicited against
consensus-based test peptides. However, there was
no significant relationship between the frequency
of a 10-mer in the viral population and either its
frequency of recognition (Spearman's
correlation coefficient
ρ = 0.24) or the
magnitude of the responses
(ρ = 0.16). We found that
peptides with a single mutation compared to the
consensus were likely to be recognized (especially
if the change was conservative) and to elicit
responses of similar magnitude as the consensus
peptide. Our results indicate that
cross-reactivity between rare and frequent
variants is likely to play a role in the expansion
of CTL responses, and that maximizing antigenic
diversity in a vaccine may increase the breadth
and depth of CTL responses. However, since there
are few obvious preferred pathways to virologic
escape, the diversity that may be required to
block all potential escape pathways may be too
large for a realistic vaccine to accommodate.
Furthermore, since peptides were not recognized
based on their frequency in the population, it
remains unclear by which mechanisms
variability-inclusive antigens (i.e., constructs
enriched with frequent variants) expand CTL
recognition.</p>
</div>
</front>
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</div1>
</back>
</TEI>
<affiliations><list><country><li>Espagne</li>
<li>États-Unis</li>
</country>
<region><li>Catalogne</li>
<li>Massachusetts</li>
<li>Washington (État)</li>
</region>
<settlement><li>Barcelone</li>
<li>Seattle</li>
</settlement>
<orgName><li>Université de Washington</li>
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</list>
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<name sortKey="Allen, Todd M" sort="Allen, Todd M" uniqKey="Allen T" first="Todd M." last="Allen">Todd M. Allen</name>
<name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name>
<name sortKey="Deng, Wenjie" sort="Deng, Wenjie" uniqKey="Deng W" first="Wenjie" last="Deng">Wenjie Deng</name>
<name sortKey="Frahm, Nicole" sort="Frahm, Nicole" uniqKey="Frahm N" first="Nicole" last="Frahm">Nicole Frahm</name>
<name sortKey="Heckerman, David E" sort="Heckerman, David E" uniqKey="Heckerman D" first="David E." last="Heckerman">David E. Heckerman</name>
<name sortKey="Mullins, James I" sort="Mullins, James I" uniqKey="Mullins J" first="James I." last="Mullins">James I. Mullins</name>
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<name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name>
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</tree>
</affiliations>
</record>
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