TCRMatch: Predicting T-Cell Receptor Specificity Based on Sequence Similarity to Previously Characterized Receptors.

TCRMatch: Predicting T-Cell Receptor Specificity Based on Sequence Similarity to Previously Characterized Receptors.
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DOI:
10.3389/fimmu.2021.640725
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发表时间:
2021
影响因子:
7.3
通讯作者:
Peters B
Peters B
中科院分区:
医学2区
文献类型:
--
作者:
Chronister WD;Crinklaw A;Mahajan S;Vita R;Koşaloğlu-Yalçın Z;Yan Z;Greenbaum JA;Jessen LE;Nielsen M;Christley S;Cowell LG;Sette A;Peters B

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脊椎动物的适应性免疫系统已经进化到识别非自身抗原,如由感染性病原体和突变的癌细胞表达的蛋白质。T细胞在抗原识别中发挥着重要的作用,它表达一系列抗原特异性受体,这些受体与抗原表位结合,从而启动靶向免疫反应。高通量测序的最新进展使T细胞受体(TCR)谱系数据的常规生成成为可能。确定这些数据中不同TCR所针对的特定表位将是有价值的。为了做到这一点,我们利用了自2004年以来在免疫表位数据库(IEDB)中收集的具有已知表位特异性的TCR数量不断增加的优势。我们比较了7个序列相似性指标,以确定它们预测两个TCR是否具有相同的表位特异性的能力。我们发现,综合的k-mer匹配方法产生了最好的结果,我们已经在TCRMatch中实现了这一方法,TCRMatch是一个开放可访问的工具(http://tools.iedb.org/tcrmatch/)),它以TCRIEDB中的β链CDR3序列为输入,识别TCR与IEDB中的匹配,并报告每个匹配的特异性。我们预计,该工具将为受体谱系和单细胞测序实验中捕获的T细胞反应提供新的见解,并将促进监测和治疗传染病、过敏性疾病、自身免疫性疾病以及癌症的新策略的开发。
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.
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