Zeynep Koşaloğlu

The adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. Identifying the specific epitopes targeted by different TCRs in these data would be valuable. To accomplish that, we took advantage of the ever-increasing number of TCRs with known epitope specificity curated in the Immune Epitope Database (IEDB) since 2004. We compared seven metrics of sequence similarity to determine their power to predict if two TCRs have the same epitope specificity. We found that a comprehensive k -mer matching approach produced the best results, which we have implemented into TCRMatch, an openly accessible tool ( http://tools.iedb.org/tcrmatch/ ) that takes TCR β-chain CDR3 sequences as an input, identifies TCRs with a match in the IEDB, and reports the specificity of each match. We anticipate that this tool will provide new insights into T cell responses captured in receptor repertoire and single cell sequencing experiments and will facilitate the development of new strategies for monitoring and treatment of infectious, allergic, and autoimmune diseases, as well as cancer.

SNV: single nucleotide variant; nsSNV: nonsynonymous single nucleotide variant; ROC: receiver operating characteristic; AUC: area under ROC curve; HLA: human leukocyte antigen; MHC: major histocompatibility complex; PD-1: Programmed cell death protein 1; PD-L1 or CTLA-4: cytotoxic T-lymphocyte associated protein 4.

We established The Cancer Epitope Database and Analysis Resource (CEDAR) to catalog all epitope data in the context of cancer. The specific molecular targets of adaptive T cell and B cell immune responses are referred to as epitopes. Epitopes derived from cancer antigens are of high relevance as they are recognized by anti-cancer immune cells. Detailed knowledge of the molecular characteristic of cancer epitopes and associated metadata is relevant to understanding and planning prophylactic and therapeutic applications and accurately characterizing naturally occurring immune responses and cancer immunopathology. CEDAR provides a freely accessible, comprehensive collection of cancer epitope and receptor data curated from the literature and serves as a companion site to the Immune Epitope Database (IEDB), which is focused on infectious, autoimmune, and allergic diseases. CEDAR is freely accessible at https://cedar.iedb.org/.

The Next-Generation (NG) IEDB Tools website (https://nextgen-tools.iedb.org) provides users with a redesigned interface to many of the algorithms for epitope prediction and analysis that were originally released on the legacy IEDB Tools website. The initial release focuses on consolidation of all tools related to HLA class I epitopes (MHC binding, elution, immunogenicity, and processing), making all of these predictions accessible from a single application and allowing for their simultaneous execution with minimal user inputs. Additionally, the PEPMatch tool for identifying highly similar epitopes in a set of curated proteomes, as well as a tool for epitope clustering, are available on the site. The NG Tools site allows users to build data pipelines by sending the output of one tool as input for the next. Over the next several years, all pre-existing IEDB Tools, and any newly developed tools, will be integrated into this new site. Here we describe the philosophy behind the redesign and demonstrate the utility and productivity enhancements that are enabled by the new interface.