Research Article Automatic Generation of Validated Specific Epitope Sets Sebastian Carrasco Pro, 1,2 John Sidney, 2 Sinu Paul, 2 Cecilia Lindestam Arlehamn, 2 Daniela Weiskopf, 2 Bjoern Peters, 2 and Alessandro Sette 2 1 Laboratorio de Bioinform´ atica y Biolog´ ıa Molecular, Laboratorios de Investigaci´ on y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Peru 2 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA Correspondence should be addressed to Alessandro Sette; alex@liai.org Received 24 December 2014; Accepted 2 March 2015 Academic Editor: Pedro A. Reche Copyright © 2015 Sebastian Carrasco Pro et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Accurate measurement of B and T cell responses is a valuable tool to study autoimmunity, allergies, immunity to pathogens, and host-pathogen interactions and assist in the design and evaluation of T cell vaccines and immunotherapies. In this context, it is desirable to elucidate a method to select validated reference sets of epitopes to allow detection of T and B cells. However, the ever- growing information contained in the Immune Epitope Database (IEDB) and the diferences in quality and subjects studied between epitope assays make this task complicated. In this study, we develop a novel method to automatically select reference epitope sets according to a categorization system employed by the IEDB. From the sets generated, three epitope sets (EBV, mycobacteria and dengue) were experimentally validated by detection of T cell reactivity ex vivo from human donors. Furthermore, a web application that will potentially be implemented in the IEDB was created to allow users the capacity to generate customized epitope sets. 1. Introduction Adaptive immunity is based on the recognition of specifc molecular structures, named epitopes, by either antibodies/B cell receptors or T cell receptors. Antibodies and B cell recep- tors bind a wide variety of structures, including proteins and carbohydrates. In the case of protein ligands, antibodies can recognize either a series of contiguous residues (linear epitopes) or a set of residues encoded in disparate regions of the protein sequence and brought together in the three dimensional structure of the protein ligand (discontinuous epitopes). T cells recognize a complex between MHC molecules (named HLA in humans and H-2 in mouse) and, in most cases, a peptidic epitope of 8–16 residues in length [1, 2]. T cell responses are a key component of adaptive immunity. In concert with antibody responses, CD8 T cells, recognizing class I binding epitopes, and CD4 T cells, recognizing their class II counterparts, are key players in immunity to viruses and bacteria [3]. In the case of allergic reactions, CD4 T cell responses play a key role in pathogenesis both directly and indirectly through the regulation of antibody responses of the Ig E class [4]. Accurate measurement of B and T cell responses is a valuable tool to study autoimmunity, allergies, immunity to pathogens, and host-pathogen interactions and assist in the design and evaluation of T cell-based vaccines and immunotherapies [5–8]. Accordingly, a large number of studies have been devoted to defning B and T cell epitopes, a process that has been facilitated by an ever-increasing expansion and refnement of experimental methods. As immune investigations proceed over time, many dif- ferent epitopes from various organisms have been identifed. Alternatively, large-scale epitope identifcation can reveal hundreds of potential epitopes [9–12]. Te Immune Epitope Database (IEDB) [13, 14] is a freely available resource that serves as a repository of experimentally derived immune epitope information available in the peer-reviewed published literature, as well as from direct submission from NIH-NIAID funded large-scale epitope identifcation studies. Te IEDB content covers a broad range of indications, to include infec- tious diseases (excluding HIV), allergies, transplantation, and Hindawi Publishing Corporation Journal of Immunology Research Volume 2015, Article ID 763461, 11 pages http://dx.doi.org/10.1155/2015/763461