Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus
<p>Abstract</p> <p>Background</p> <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 co...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2006-12-01
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| Series: | BMC Bioinformatics |
| Online Access: | http://dx.doi.org/10.1186/1471-2105-7-S5-S4 |
| _version_ | 1818531213023903744 |
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| author | Srinivasan KN Lee Kenneth X Heiny AT Khan Asif M Tan Tin August J Thomas Brusic Vladimir |
| author_facet | Srinivasan KN Lee Kenneth X Heiny AT Khan Asif M Tan Tin August J Thomas Brusic Vladimir |
| author_sort | Srinivasan KN |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <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> <p>Results</p> <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> <p>Conclusion</p> <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> |
| first_indexed | 2024-12-11T17:29:31Z |
| format | Article |
| id | doaj.art-f8831640766e4d1ab85a9ba2d7d60787 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-11T17:29:31Z |
| publishDate | 2006-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-f8831640766e4d1ab85a9ba2d7d607872022-12-22T00:56:52ZengBMCBMC Bioinformatics1471-21052006-12-017Suppl 5S410.1186/1471-2105-7-S5-S4Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virusSrinivasan KNLee Kenneth XHeiny ATKhan Asif MTan TinAugust J ThomasBrusic Vladimir<p>Abstract</p> <p>Background</p> <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> <p>Results</p> <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> <p>Conclusion</p> <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>http://dx.doi.org/10.1186/1471-2105-7-S5-S4 |
| spellingShingle | Srinivasan KN Lee Kenneth X Heiny AT Khan Asif M Tan Tin August J Thomas Brusic Vladimir Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus BMC Bioinformatics |
| title | Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus |
| title_full | Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus |
| title_fullStr | Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus |
| title_full_unstemmed | Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus |
| title_short | Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus |
| title_sort | large scale analysis of antigenic diversity of t cell epitopes in dengue virus |
| url | http://dx.doi.org/10.1186/1471-2105-7-S5-S4 |
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