Background: Protein antigens and their specific epitopes are formulation targets for epitopebased vaccines. A number of prediction servers are available for identification of peptides that bind major histocompatibility complex class I (MHC-I) molecules. The lack of standardized methodology and large number of human MHC-I molecules make the selection of appropriate prediction servers difficult. This study reports a comparative evaluation of thirty prediction servers for seven human MHC-I molecules.
Background: Initiation and regulation of immune responses in humans involves recognition of peptides presented by human leukocyte antigen class II (HLA-II) molecules. These peptides (HLA-II T-cell epitopes) are increasingly important as research targets for the development of vaccines and immunotherapies. HLA-II peptide binding studies involve multiple overlapping peptides spanning individual antigens, as well as complete viral proteomes. Antigen variation in pathogens and tumor antigens, and extensive polymorphism of HLA molecules increase the number of targets for screening studies. Experimental screening methods are expensive and time consuming and reagents are not readily available for many of the HLA class II molecules. Computational prediction methods complement experimental studies, minimize the number of validation experiments, and significantly speed up the epitope mapping process. We collected test data from four independent studies that involved 721 peptide binding assays. Full overlapping studies of four antigens identified binding affinity of 103 peptides to seven common HLA-DR molecules (DRB1*0101, 0301, 0401, 0701, 1101, 1301, and 1501). We used these data to analyze performance of 21 HLA-II binding prediction servers accessible through the WWW.
Tumor T cell antigens are both diagnostically and therapeutically valuable molecules. A large number of new peptides are examined as potential tumor epitopes each year, yet there is no infrastructure for storing and accessing the results of these experiments. We have retroactively cataloged more than 1000 tumor peptides from 368 different proteins, and implemented a web-accessible infrastructure for storing and accessing these experimental results. All peptides in TANTIGEN are labeled as one of the four categories: (1) peptides measured in vitro to bind the HLA, but not reported to elicit either in vivo or in vitro T cell response, (2) peptides found to bind the HLA and to elicit an in vitro T cell response, (3) peptides shown to elicit in vivo tumor rejection, and (4) peptides processed and naturally presented as defined by physical detection. In addition to T cell response, we also annotate peptides that are naturally processed HLA binders, e.g., peptides eluted from HLA in mass spectrometry studies. TANTIGEN provides a rich data resource for tumor-associated epitope and neoepitope discovery studies and is freely available at http://cvc.dfci.harvard.edu/tantigen/ or http://projects.met-hilab.org/tadb (mirror).
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