title: Transporter associated with antigen processing preselection of peptides binding to the MHC: a bioinformatic evaluation.
abstract: TAP is responsible for the transit of peptides from the cytosol to the lumen of the endoplasmic reticulum. In an immunological context, this event is followed by the binding of peptides to MHC molecules before export to the cell surface and recognition by T cells. Because TAP transport precedes MHC binding, TAP preferences may make a significant contribution to epitope selection. To assess the impact of this preselection, we have developed a scoring function for TAP affinity prediction using the additive method, have used it to analyze and extend the TAP binding motif, and have evaluated how well this model acts as a preselection step in predicting MHC binding peptides. To distinguish between MHC alleles that are exclusively dependent on TAP and those exhibiting only a partial dependence on TAP, two sets of MHC binding peptides were examined: HLA-A*0201 was selected as a representative of partially TAP-dependent HLA alleles, and HLA-A*0301 represented fully TAP-dependent HLA alleles. TAP preselection has a greater impact on TAP-dependent alleles than on TAP-independent alleles. The reduction in the number of nonbinders varied from 10% (TAP-independent) to 33% (TAP-dependent), suggesting that TAP preselection is an important component in the successful in silico prediction of T cell epitopes.
authors.affiliation: Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom.
authors.forename: Irini
authors.initials: I
authors.lastname: Doytchinova
authors.forename: Shelley
authors.initials: S
authors.lastname: Hemsley
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000483:Alleles; D017951:Antigen Presentation; D019295:Computational Biology / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism*; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D006801:Humans; D018448:Models, Immunological; D009842:Oligopeptides / Q000378:metabolism*; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000276:immunology; D025941:Protein Interaction Mapping / Q000379:methods* / Q000706:statistics & numerical data; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; C442141:HLA-A*03:01 antigen; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D009842:Oligopeptides; C073119:TAP1 protein, human; C071692:TAP2 protein, human