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HLArestrictor - a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides
Malene Erup Larsen1, Henrik Kloverpris2, Annette Stryhn3, Catherine K. Koofhethile2, Stuart Sims2,
Thumbi Ndung'u4,5, Philip Goulder2, Soren Buus, and Morten Nielsen1 Immunogenetics. 2010 Nov 16. [Epub ahead of print]

1Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
2University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, OX1 3SY, Oxford, England
3Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Denmark
4HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
5Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Charlestown, MA, 02129, USA

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 IFN# 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.

PMID: 21079948

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Morten Nielsen,