title: HLArestrictor--a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides.
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.
authors.affiliation: Center for Biological Sequence Analysis, DTU Systems Biology, Building 208, Technical University of Denmark, DK-2800, Lyngby, Denmark. mel@cbs.dtu.dk
authors.forename: Malene
authors.initials: M
authors.lastname: Erup Larsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Kloverpris
authors.forename: Anette
authors.initials: A
authors.lastname: Stryhn
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Koofhethile
authors.forename: Stuart
authors.initials: S
authors.lastname: Sims
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.forename: Søren
authors.initials: S
authors.lastname: Buus
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
mesh_terms: D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015331:Cohort Studies; D030562:Databases, Protein; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping / Q000706:statistics & numerical data; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D012984:Software
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010455:Peptides; D007371:Interferon-gamma