RT Journal Article
SR Electronic
T1 TCRMatch: Predicting T-cell receptor specificity based on sequence similarity to previously characterized receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.11.418426
DO 10.1101/2020.12.11.418426
A1 William D. Chronister
A1 Austin Crinklaw
A1 Swapnil Mahajan
A1 Randi Vita
A1 Zeynep Kosaloglu-Yalcin
A1 Zhen Yan
A1 Jason A. Greenbaum
A1 Leon E. Jessen
A1 Morten Nielsen
A1 Scott Christley
A1 Lindsay G. Cowell
A1 Alessandro Sette
A1 Bjoern Peters
YR 2020
UL http://biorxiv.org/content/early/2020/12/11/2020.12.11.418426.abstract
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.