![]() ![]() While TCR repertoire sequencing can track perturbations in the composition of antigen-specific T cell populations, it does not yield information on which TCRs are recognizing which epitopes. All of the main TCR repertoire sequencing approaches in use today generate information about the CDR3 region in the TCR β chain, as that part of the TCR is thought to convey the most information about TCR specificity and can serve as a “barcode” to track T cells with different specificities. Single cell sequencing with targeted TCR identification, as provided by, for example, the 10x Genomics technology platform ( 6), identifies the gene expression state of individual T cells, along with the receptor sequences that-in principle-indicate the specificity of these T cells. Using different next-generation sequencing and bioinformatics approaches, TCRs can be sequenced to different levels of resolution, ranging from paired sequencing of full α and β chains to partial sequencing of the TCR β chain by itself. TCR repertoire sequencing has emerged as an accessible and efficient approach to capture the diversity of TCRs in blood or tissue samples of an individual ( 5). The varying antigen specificity of different TCRs allows T cells to initiate immune responses against a broad and ever-changing range of non-self entities, including infectious agents and mutated cancer cells. Broadly speaking, CDR3 directly interacts with the presented peptide, while CDR1 and CDR2 primarily interact with the MHC molecule ( 4). The specificity of a given TCR is dependent upon the amino acid sequence of each chain, particularly the three highly polymorphic complementarity-determining regions (CDR1, CDR2, CDR3). Different TCRs are capable of recognizing different epitopes presented by major histocompatibility (MHC) class I or class II proteins on the cell surface ( 3). ![]() Each T cell expresses a characteristic T-cell receptor (TCR) typically consisting of an α and β chain, which are formed during T cell maturation as a result of stochastic V(D)J gene recombination ( 2). T cells are lymphocytes that play a critical role in the function of the adaptive immune system ( 1). 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. We found that a comprehensive k-mer matching approach produced the best results, which we have implemented into TCRMatch, an openly accessible tool ( ) 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 compared seven metrics of sequence similarity to determine their power to predict if two TCRs have the same epitope specificity. 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. Identifying the specific epitopes targeted by different TCRs in these data would be valuable. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. 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. The adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. 5Department of Medicine, University of California, San Diego, San Diego, CA, United States.4Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, United States.3Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, Argentina.2Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Lyngby, Denmark.1La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.Cowell 4 Alessandro Sette 1,5 Bjoern Peters 1,5 * Jessen 2 Morten Nielsen 2,3 Scott Christley 4 Lindsay G. ![]() Chronister 1 † Austin Crinklaw 1 † Swapnil Mahajan 1 Randi Vita 1 Zeynep Koşaloğlu-Yalçın 1 Zhen Yan 1 Jason A. ![]()
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