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Immunogenetics

, Volume 63, Issue 1, pp 43–55 | Cite as

HLArestrictor—a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides

  • Malene Erup Larsen
  • Henrik Kloverpris
  • Anette Stryhn
  • Catherine K. Koofhethile
  • Stuart Sims
  • Thumbi Ndung’u
  • Philip Goulder
  • Søren Buus
  • Morten Nielsen
Original Paper

Abstract

Traditionally, T cell epitope discovery requires considerable amounts of tedious, slow, and costly experimental work. During the last decade, prediction tools have emerged as essential tools allowing researchers to select a manageable list of epitope candidates to test from a larger peptide, protein, or even proteome. However, no current tools address the complexity caused by the highly polymorphic nature of the restricting HLA molecules, which effectively individualizes T cell responses. To fill this gap, we here present an easy-to-use prediction tool named HLArestrictor (http://www.cbs.dtu.dk/services/HLArestrictor), which is based on the highly versatile and accurate NetMHCpan predictor, which here has been optimized for the identification of both the MHC restriction element and the corresponding minimal epitope of a T cell response in a given individual. As input, it requires high-resolution (i.e., 4-digit) HLA typing of the individual. HLArestrictor then predicts all 8–11mer peptide binders within one or more larger peptides and provides an overview of the predicted HLA restrictions and minimal epitopes. The method was tested on a large dataset of HIV IFNγ ELIspot peptide responses and was shown to identify HLA restrictions and minimal epitopes for about 90% of the positive peptide/patient pairs while rejecting more than 95% of the negative peptide-HLA pairs. Furthermore, for 18 peptide/HLA tetramer validated responses, HLArestrictor in all cases predicted both the HLA restriction element and minimal epitope. Thus, HLArestrictor should be a valuable tool in any T cell epitope discovery process aimed at identifying new epitopes from infectious diseases and other disease models.

Keywords

HLA restriction Epitope prediction MHC class I Peptide binding T cell epitope validation HLA tetramer validation 

Notes

Acknowledgements

This work was supported by a NIH (National Institute of Health) grant (contract no. HHSN272200900045C) and The Danish Council for Independent Research Technology and Production Sciences (FTP 274-05-0582).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Malene Erup Larsen
    • 1
  • Henrik Kloverpris
    • 2
  • Anette Stryhn
    • 3
  • Catherine K. Koofhethile
    • 2
  • Stuart Sims
    • 2
  • Thumbi Ndung’u
    • 4
    • 5
  • Philip Goulder
    • 2
  • Søren Buus
    • 3
  • Morten Nielsen
    • 1
  1. 1.Center for Biological Sequence Analysis, DTU Systems Biology, Building 208Technical University of DenmarkLyngbyDenmark
  2. 2.Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUK
  3. 3.Laboratory of Experimental Immunology, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark
  4. 4.HIV Pathogenesis Programme, Doris Duke Medical Research InstituteUniversity of KwaZulu-NatalDurbanSouth Africa
  5. 5.Ragon Institute of Massachusetts General HospitalMassachusetts Institute of Technology and Harvard UniversityCharlestownUSA

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