PT - JOURNAL ARTICLE AU - William D. Chronister AU - Austin Crinklaw AU - Swapnil Mahajan AU - Randi Vita AU - Zeynep Kosaloglu-Yalcin AU - Zhen Yan AU - Jason A. Greenbaum AU - Leon E. Jessen AU - Morten Nielsen AU - Scott Christley AU - Lindsay G. Cowell AU - Alessandro Sette AU - Bjoern Peters TI - TCRMatch: Predicting T-cell receptor specificity based on sequence similarity to previously characterized receptors AID - 10.1101/2020.12.11.418426 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.12.11.418426 4099 - http://biorxiv.org/content/early/2020/12/11/2020.12.11.418426.short 4100 - http://biorxiv.org/content/early/2020/12/11/2020.12.11.418426.full AB - 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 six 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.Competing Interest StatementThe authors have declared no competing interest.