An integrative approach to CTL epitope prediction: a combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions.
Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have also been developed for predicting the antigen-processing steps preceding MHC class I binding, including proteasomal cleavage and transporter associated with antigen processing (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI database to show that a method integrating predictions of MHC class I binding affinity, TAP transport efficiency, and C-terminal proteasomal cleavage outperforms any of the individual methods. Using an independent evaluation dataset of HIV epitopes from the Los Alamos database, the validity of the integrated method is confirmed. The performance of the integrated method is found to be significantly higher than that of the two publicly available prediction methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset, 9% and 10% of all possible nonamers in the HIV proteins must be tested when using the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate epitopes. This number is reduced to 7% when using the integrated method. In practical terms, this means that the experimental effort needed to identify an epitope in a hypothetical protein with 85% probability is reduced by 20-30% when using the integrated method. The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php.
Larsen
Mette Voldby
MV
Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark.
Lundegaard
Claus
C
Lamberth
Kasper
K
Buus
Søren
S
Brunak
Søren
S
Lund
Ole
O
Nielsen
Morten
M
D018528:ATP-Binding Cassette Transporters; D000465:Algorithms; D003627:Data Interpretation, Statistical; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D011237:Predictive Value of Tests; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C477327:transporter associated with antigen processing (TAP); D046988:Proteasome Endopeptidase Complex