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

TY - JOUR

T1 - HLArestrictor--a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides

AU - Erup Larsen, Malene

AU - Kloverpris, Henrik

AU - Buus, Anette Stryhn

AU - Koofhethile, Catherine K

AU - Sims, Stuart

AU - Ndung'u, Thumbi

AU - Goulder, Philip

AU - Buus, Søren

AU - Nielsen, Morten

PY - 2011/1

Y1 - 2011/1

N2 - 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 AR 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.

AB - 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 AR 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.

KW - Amino Acid Sequence

KW - CD8-Positive T-Lymphocytes

KW - Cell Line

KW - Cohort Studies

KW - Databases, Protein

KW - Enzyme-Linked Immunospot Assay

KW - Epitope Mapping

KW - Epitopes, T-Lymphocyte

KW - HIV Infections

KW - HLA Antigens

KW - Humans

KW - Interferon-gamma

KW - Molecular Sequence Data

KW - Peptides

KW - Software

U2 - 10.1007/s00251-010-0493-5

DO - 10.1007/s00251-010-0493-5

M3 - Journal article

C2 - 21079948

SN - 0093-7711

VL - 63

SP - 43

EP - 55

JO - Immunogenetics

JF - Immunogenetics

IS - 1

ER -