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This article is part of the supplement: APBioNet – Fifth International Conference on Bioinformatics (InCoB2006)

Open Access Proceedings

Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus

Asif M Khan12, AT Heiny13, Kenneth X Lee12, KN Srinivasan14, Tin Wee Tan3, J Thomas August14 and Vladimir Brusic25*

Author Affiliations

1 The Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01 The Nanos, Singapore 138669, Singapore

2 Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore

3 Department of Biochemistry, The Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore

4 Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA

5 School of Land and Food Sciences, and Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia

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BMC Bioinformatics 2006, 7(Suppl 5):S4  doi:10.1186/1471-2105-7-S5-S4

Published: 18 December 2006

Abstract

Background

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.

Results

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).

Conclusion

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).