Discovery of Conserved Epitopes Through Sequence Variability Analyses

  • Carmen M. Díez-Rivero
  • Pedro RecheEmail author
Part of the Immunomics Reviews: book series (IMMUN, volume 3)


Sequence variation is a common theme used by a variety of human pathogens, including the Human Immunodeficiency Virus (HIV-1), to escape the host immune response. Therefore, under such scenario, a successful vaccine should be based on antigenic determinants lying within conserved protein antigen regions. This chapter will illustrate the application of sequence variability analyses to the identification of such conserved regions and/or epitopes using the Protein Variability Server (PVS). PVS is a web-based tool that compute the absolute site variability in protein antigens from the relevant multiple protein-sequence alignments (MSAs). In addition, PVS has been tuned to facilitate the design of epitope-based vaccines. Specifically, PVS enables the prediction of conserved T cell epitopes by generating a variability-masked sequence that can be submitted to the RANKPEP T cell epitope prediction tool. Moreover, PVS allows the identification of conserved fragments that are surface exposed and thus potential targets of the humoral response.


Cell Epitope Antigenic Determinant Shannon Diversity Index Sequence Variability Protein Variability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The work and the authors were supported by grant SAF2006-07879 from the “Ministerio de Educación y Ciencia” of Spain to PR.


  1. Disis ML, Knutson KL, McNeel DG et al (2001) Clinical translation of peptide-based vaccine trials: The HER-2/neumodel. Crit Rev Immunol 21:263–274PubMedGoogle Scholar
  2. Edgar RC (2004) MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797CrossRefPubMedGoogle Scholar
  3. García-Boronat M, Diez-Rivero CM, Reinherz EL et al (2008) PVS: A web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery. Nucleic Acids Res 36:W35–W41CrossRefPubMedGoogle Scholar
  4. Mendis KN, David PH, Carter R (1991) Antigenic polymorphism in malaria: Is it an important mechanism for immune evasion? Immunol Today 12:A34–A37CrossRefPubMedGoogle Scholar
  5. Phillips RE, Rowland-Jones S et al (1991) Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354:453–459CrossRefPubMedGoogle Scholar
  6. Reche PA, Reinherz EL (2003) Sequence variability analysis of human class I and class II MHC molecules: Functional and structural correlates of amino acid polymorphisms. J Mol Biol 331:623–641CrossRefPubMedGoogle Scholar
  7. Reche PA, Reinherz EL (2007) Prediction of peptide-MHC binding using profiles. Mol Biol 409:185–200Google Scholar
  8. Reche PA, Glutting JP, Reinherz EL (2002) Prediction of MHC class I binding peptides using profile motifs. Hum Immunol 63:701–709CrossRefPubMedGoogle Scholar
  9. Reche PA, Glutting J-P, Reinherz EL (2004) Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics 56:405–419CrossRefPubMedGoogle Scholar
  10. Reche PA, Keskin DB, Hussey RE et al (2006) Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes. Med Immunol 5:1CrossRefPubMedGoogle Scholar
  11. Sette A, Newman M, Livingston B et al (2002) Optimizing vaccine design for cellular processing, MHC binding and TCR recognition. Tissue Antigens 59:443–451CrossRefPubMedGoogle Scholar
  12. Shannon CE (1948) The mathematical theory of communication. Bell Syst Tech J 27(379–423):623–656Google Scholar
  13. Simpson EH (1949) Measurement of diversity. Nature 163:688CrossRefGoogle Scholar
  14. Thomsona SA, Jaramillo AB, Shoobridge M et al (2005) Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine designed for global use. Vaccine 23:4647–4657CrossRefGoogle Scholar
  15. Tsuji M, Zavala F (2001) Peptide-based subunit vaccines against preerythrocytic stages of malaria parasites. Mol Immunol 38:433–442CrossRefPubMedGoogle Scholar
  16. Weber F, Elliott RM (2002) Antigenic drift, antigenic shift and interferon antagonists: How bunyaviruses counteract the immune system. Virus Res 88:129–136CrossRefPubMedGoogle Scholar
  17. Wu TT, Kabat EA (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med 132:211–250CrossRefPubMedGoogle Scholar
  18. Zolla-Pazner S (2004) Identifying epitopes of HIV-1 that induce protective antibodies. Nat Rev Immunol 4:199–210CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Facultad de Medicina, Departamento de Immunología (Microbiología I)Universidad Complutense de MadridMadridSpain

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