title: Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes.
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.
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. Electronic address: spaul@liai.org.
authors: Sinu
authors: S
authors: Paul
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Cecilia S
authors: CS
authors: Lindestam Arlehamn
authors: South African Tuberculosis Vaccine Initiative (SATVI), School of Child and Adolescent Health, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Thomas J
authors: TJ
authors: Scriba
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Myles B C
authors: MB
authors: Dillon
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Carla
authors: C
authors: Oseroff
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Denise
authors: D
authors: Hinz
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Denise M
authors: DM
authors: McKinney
authors: Laboratorio de Bioinformática y Biología Molecular, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors: Sebastian
authors: S
authors: Carrasco Pro
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: John
authors: J
authors: Sidney
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Bjoern
authors: B
authors: Peters
authors: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Alessandro
authors: A
authors: Sette
mesh_terms: D000465:Algorithms; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000276:immunology; D059826:HLA-DRB3 Chains / Q000276:immunology; D059845:HLA-DRB4 Chains / Q000276:immunology; D059847:HLA-DRB5 Chains / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D059847:HLA-DRB5 Chains; D000949:Histocompatibility Antigens Class II; D010455:Peptides
keywords: Epitope prediction; HLA class II restricted T cell epitopes