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Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes

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dc.contributor.author Paul, Sinu
dc.contributor.author Lindestam Arlehamn, Cecilia S.
dc.contributor.author Scriba, Thomas J.
dc.contributor.author Dillon, Myles B. C.
dc.contributor.author Oseroff, Carla
dc.contributor.author Hinz, Denise
dc.contributor.author McKinney, Denise M.
dc.contributor.author Carrasco Pro, Sebastian
dc.contributor.author Sidney, John
dc.contributor.author Peters, Bjoern
dc.contributor.author Sette, Alessandro
dc.date.accessioned 2019-02-06T14:52:40Z
dc.date.available 2019-02-06T14:52:40Z
dc.date.issued 2015
dc.identifier.uri https://hdl.handle.net/20.500.12866/5351
dc.description.abstract Computational prediction of HLA class II restricted T cell epitopes has great significance in many immunological studies including vaccine discovery. In recent years, prediction of HLA class II binding has improved significantly but a strategy to globally predict the most dominant epitopes has not been rigorously defined. Using human immunogenicity data associated with sets of 15-mer peptides overlapping by 10 residues spanning over 30 different allergens and bacterial antigens, and HLA class II binding prediction tools from the Immune Epitope Database and Analysis Resource (IEDB), we optimized a strategy to predict the top epitopes recognized by human populations. The most effective strategy was to select peptides based on predicted median binding percentiles for a set of seven DRB1 and DRB3/4/5 alleles. These results were validated with predictions on a blind set of 15 new allergens and bacterial antigens. We found that the top 21% predicted peptides (based on the predicted binding to seven DRB1 and DRB3/4/5 alleles) were required to capture 50% of the immune response. This corresponded to an IEDB consensus percentile rank of 20.0, which could be used as a universal prediction threshold. Utilizing actual binding data (as opposed to predicted binding data) did not appreciably change the efficacy of global predictions, suggesting that the imperfect predictive capacity is not due to poor algorithm performance, but intrinsic limitations of HLA class II epitope prediction schema based on HLA binding in genetically diverse human populations. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof urn:issn:1872-7905
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject Algorithms en_US
dc.subject Epitope Mapping en_US
dc.subject Epitope prediction en_US
dc.subject Epitopes, T-Lymphocyte/immunology en_US
dc.subject Histocompatibility Antigens Class II/immunology en_US
dc.subject HLA class II restricted T cell epitopes en_US
dc.subject HLA-DRB1 Chains/immunology en_US
dc.subject HLA-DRB3 Chains/immunology en_US
dc.subject HLA-DRB4 Chains/immunology en_US
dc.subject HLA-DRB5 Chains/immunology en_US
dc.subject Peptides/immunology en_US
dc.subject Protein Binding/immunology en_US
dc.title Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.jim.2015.03.022
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.03

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