Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus
Identifieur interne : 002D10 ( Main/Exploration ); précédent : 002D09; suivant : 002D11Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus
Auteurs : Asif M. Khan [Singapour] ; At Heiny [Singapour] ; Kenneth X. Lee [Singapour] ; Kn Srinivasan [Singapour, États-Unis] ; Tin Wee Tan [Singapour] ; J Thomas August [Singapour, États-Unis] ; Vladimir Brusic [Singapour, Australie]Source :
- BMC Bioinformatics [ 1471-2105 ] ; 2006.
Descripteurs français
- KwdFr :
- Bases de données de protéines, Biologie informatique (), Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T (analyse), Fragments peptidiques (immunologie), Protéines virales (immunologie), Similitude de séquences d'acides aminés, Séquence d'acides aminés, Sérotypage, Variation des antigènes, Virus de la dengue (immunologie).
- MESH :
- analyse : Déterminants antigéniques des lymphocytes T.
- immunologie : Fragments peptidiques, Protéines virales, Virus de la dengue.
- Bases de données de protéines, Biologie informatique, Données de séquences moléculaires, Similitude de séquences d'acides aminés, Séquence d'acides aminés, Sérotypage, Variation des antigènes.
English descriptors
- KwdEn :
- MESH :
- chemical , analysis : Epitopes, T-Lymphocyte.
- immunology : Dengue Virus, Peptide Fragments, Viral Proteins.
- methods : Computational Biology.
- Amino Acid Sequence, Antigenic Variation, Databases, Protein, Molecular Sequence Data, Sequence Homology, Amino Acid, Serotyping.
Abstract
Antigenic diversity in dengue virus strains has been studied, but large-scale and detailed systematic analyses have not been reported. In this study, we report a bioinformatics method for analyzing viral antigenic diversity in the context of T-cell mediated immune responses. We applied this method to study the relationship between short-peptide antigenic diversity and protein sequence diversity of dengue virus. We also studied the effects of sequence determinants on viral antigenic diversity. Short peptides, principally 9-mers were studied because they represent the predominant length of binding cores of T-cell epitopes, which are important for formulation of vaccines.
Our analysis showed that the number of unique protein sequences required to represent complete antigenic diversity of short peptides in dengue virus is significantly smaller than that required to represent complete protein sequence diversity. Short-peptide antigenic diversity shows an asymptotic relationship to the number of unique protein sequences, indicating that for large sequence sets (~200) the addition of new protein sequences has marginal effect to increasing antigenic diversity. A near-linear relationship was observed between the extent of antigenic diversity and the length of protein sequences, suggesting that, for the practical purpose of vaccine development, antigenic diversity of short peptides from dengue virus can be represented by short regions of sequences (~<100 aa) within viral antigens that are specific targets of immune responses (such as T-cell epitopes specific to particular human leukocyte antigen alleles).
This study provides evidence that there are limited numbers of antigenic combinations in protein sequence variants of a viral species and that short regions of the viral protein are sufficient to capture antigenic diversity of T-cell epitopes. The approach described herein has direct application to the analysis of other viruses, in particular those that show high diversity and/or rapid evolution, such as influenza A virus and human immunodeficiency virus (HIV).
Url:
DOI: 10.1186/1471-2105-7-S5-S4
PubMed: 17254309
PubMed Central: 1764481
Affiliations:
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type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Tan, Tin Wee" sort="Tan, Tin Wee" uniqKey="Tan T" first="Tin Wee" last="Tan">Tin Wee Tan</name><affiliation wicri:level="4"><nlm:aff id="I3">Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="August, J Thomas" sort="August, J Thomas" uniqKey="August J" first="J Thomas" last="August">J Thomas August</name><affiliation wicri:level="1"><nlm:aff id="I1">The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669</wicri:regionArea><wicri:noRegion>Singapore 138669</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="I4">Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name><affiliation wicri:level="4"><nlm:aff id="I2">Department of Microbiology, The 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Khan</name><affiliation wicri:level="1"><nlm:aff id="I1">The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669</wicri:regionArea><wicri:noRegion>Singapore 138669</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="I2">Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Heiny, At" sort="Heiny, At" uniqKey="Heiny A" first="At" last="Heiny">At Heiny</name><affiliation wicri:level="1"><nlm:aff id="I1">The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669</wicri:regionArea><wicri:noRegion>Singapore 138669</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="I3">Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lee, Kenneth X" sort="Lee, Kenneth X" uniqKey="Lee K" first="Kenneth X" last="Lee">Kenneth X. Lee</name><affiliation wicri:level="1"><nlm:aff id="I1">The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669</wicri:regionArea><wicri:noRegion>Singapore 138669</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="I2">Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Srinivasan, Kn" sort="Srinivasan, Kn" uniqKey="Srinivasan K" first="Kn" last="Srinivasan">Kn Srinivasan</name><affiliation wicri:level="1"><nlm:aff id="I1">The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669</wicri:regionArea><wicri:noRegion>Singapore 138669</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="I4">Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Tan, Tin Wee" sort="Tan, Tin Wee" uniqKey="Tan T" first="Tin Wee" last="Tan">Tin Wee Tan</name><affiliation wicri:level="4"><nlm:aff id="I3">Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="August, J Thomas" sort="August, J Thomas" uniqKey="August J" first="J Thomas" last="August">J Thomas August</name><affiliation wicri:level="1"><nlm:aff id="I1">The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669</wicri:regionArea><wicri:noRegion>Singapore 138669</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="I4">Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name><affiliation wicri:level="4"><nlm:aff id="I2">Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">School of Land and Food Sciences, and Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Land and Food Sciences, and Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD 4072</wicri:regionArea><wicri:noRegion>QLD 4072</wicri:noRegion></affiliation></author></analytic><series><title level="j">BMC Bioinformatics</title><idno type="eISSN">1471-2105</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antigenic Variation</term><term>Computational Biology (methods)</term><term>Databases, Protein</term><term>Dengue Virus (immunology)</term><term>Epitopes, T-Lymphocyte (analysis)</term><term>Molecular Sequence Data</term><term>Peptide Fragments (immunology)</term><term>Sequence Homology, Amino Acid</term><term>Serotyping</term><term>Viral Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Bases de données de protéines</term><term>Biologie informatique ()</term><term>Données de séquences moléculaires</term><term>Déterminants antigéniques des lymphocytes T (analyse)</term><term>Fragments peptidiques (immunologie)</term><term>Protéines virales (immunologie)</term><term>Similitude de séquences d'acides aminés</term><term>Séquence d'acides aminés</term><term>Sérotypage</term><term>Variation des antigènes</term><term>Virus de la dengue (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Epitopes, T-Lymphocyte</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Fragments peptidiques</term><term>Protéines virales</term><term>Virus de la dengue</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dengue Virus</term><term>Peptide Fragments</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Computational Biology</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Antigenic Variation</term><term>Databases, Protein</term><term>Molecular Sequence Data</term><term>Sequence Homology, Amino Acid</term><term>Serotyping</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Bases de données de protéines</term><term>Biologie informatique</term><term>Données de séquences moléculaires</term><term>Similitude de séquences d'acides aminés</term><term>Séquence d'acides aminés</term><term>Sérotypage</term><term>Variation des antigènes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Antigenic diversity in dengue virus strains has been studied, but large-scale and detailed systematic analyses have not been reported. In this study, we report a bioinformatics method for analyzing viral antigenic diversity in the context of T-cell mediated immune responses. We applied this method to study the relationship between short-peptide antigenic diversity and protein sequence diversity of dengue virus. We also studied the effects of sequence determinants on viral antigenic diversity. Short peptides, principally 9-mers were studied because they represent the predominant length of binding cores of T-cell epitopes, which are important for formulation of vaccines.</p></sec><sec><title>Results</title><p>Our analysis showed that the number of unique protein sequences required to represent complete antigenic diversity of short peptides in dengue virus is significantly smaller than that required to represent complete protein sequence diversity. Short-peptide antigenic diversity shows an asymptotic relationship to the number of unique protein sequences, indicating that for large sequence sets (~200) the addition of new protein sequences has marginal effect to increasing antigenic diversity. A near-linear relationship was observed between the extent of antigenic diversity and the length of protein sequences, suggesting that, for the practical purpose of vaccine development, antigenic diversity of short peptides from dengue virus can be represented by short regions of sequences (~<100 aa) within viral antigens that are specific targets of immune responses (such as T-cell epitopes specific to particular human leukocyte antigen alleles).</p></sec><sec><title>Conclusion</title><p>This study provides evidence that there are limited numbers of antigenic combinations in protein sequence variants of a viral species and that short regions of the viral protein are sufficient to capture antigenic diversity of T-cell epitopes. The approach described herein has direct application to the analysis of other viruses, in particular those that show high diversity and/or rapid evolution, such as influenza A virus and human immunodeficiency virus (HIV).</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>Singapour</li><li>États-Unis</li></country><region><li>Maryland</li></region><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Khan, Asif M" sort="Khan, Asif M" uniqKey="Khan A" first="Asif M" last="Khan">Asif M. Khan</name></noRegion><name sortKey="August, J Thomas" sort="August, J Thomas" uniqKey="August J" first="J Thomas" last="August">J Thomas August</name><name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name><name sortKey="Heiny, At" sort="Heiny, At" uniqKey="Heiny A" first="At" last="Heiny">At Heiny</name><name sortKey="Heiny, At" sort="Heiny, At" uniqKey="Heiny A" first="At" last="Heiny">At Heiny</name><name sortKey="Khan, Asif M" sort="Khan, Asif M" uniqKey="Khan A" first="Asif M" last="Khan">Asif M. Khan</name><name sortKey="Lee, Kenneth X" sort="Lee, Kenneth X" uniqKey="Lee K" first="Kenneth X" last="Lee">Kenneth X. Lee</name><name sortKey="Lee, Kenneth X" sort="Lee, Kenneth X" uniqKey="Lee K" first="Kenneth X" last="Lee">Kenneth X. Lee</name><name sortKey="Srinivasan, Kn" sort="Srinivasan, Kn" uniqKey="Srinivasan K" first="Kn" last="Srinivasan">Kn Srinivasan</name><name sortKey="Tan, Tin Wee" sort="Tan, Tin Wee" uniqKey="Tan T" first="Tin Wee" last="Tan">Tin Wee Tan</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Srinivasan, Kn" sort="Srinivasan, Kn" uniqKey="Srinivasan K" first="Kn" last="Srinivasan">Kn Srinivasan</name></region><name sortKey="August, J Thomas" sort="August, J Thomas" uniqKey="August J" first="J Thomas" last="August">J Thomas August</name></country><country name="Australie"><noRegion><name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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