The two-faced T cell epitope

Advances in the field of T cell immunology have contributed to the understanding that cross-reactivity is an intrinsic characteristic of the T cell receptor (TCR), and that each TCR can potentially interact with many different T cell epitopes. To better define the potential for TCR cross-reactivity between epitopes derived from the human genome, the human microbiome, and human pathogens, we developed a new immunoinformatics tool, JanusMatrix, that represents an extension of the validated T cell epitope mapping tool, EpiMatrix. Initial explorations, summarized in this synopsis, have uncovered what appear to be important differences in the TCR cross-reactivity of selected regulatory and effector T cell epitopes with other epitopes in the human genome, human microbiome, and selected human pathogens. In addition to exploring the T cell epitope relationships between human self, commensal and pathogen, JanusMatrix may also be useful to explore some aspects of heterologous immunity and to examine T cell epitope relatedness between pathogens to which humans are exposed (Dengue serotypes, or HCV and Influenza, for example). In Hand-Foot-Mouth disease (HFMD) for example, extensive enterovirus and human microbiome cross-reactivity (and limited cross-reactivity with the human genome) seemingly predicts immunodominance. In contrast, more extensive cross-reactivity with proteins contained in the human genome as compared to the human microbiome was observed for selected Treg epitopes. While it may be impossible to predict all immune response influences, the availability of sequence data from the human genome, the human microbiome, and an array of human pathogens and vaccines has made computationally–driven exploration of the effects of T cell epitope cross-reactivity now possible. This is the first description of JanusMatrix, an algorithm that assesses TCR cross-reactivity that may contribute to a means of predicting the phenotype of T cells responding to selected T cell epitopes. Whether used for explorations of T cell phenotype or for evaluating cross-conservation between related viral strains at the TCR face of viral epitopes, further JanusMatrix studies may contribute to developing safer, more effective vaccines.

T细胞免疫学领域的进展有助于理解交叉反应是T细胞受体（TCR）的固有特性，并且每个TCR可能与许多不同的T细胞表位相互作用。为了更好地确定源自人类基因组、人类微生物组和人类病原体的表位之间TCR交叉反应的可能性，我们开发了一种新的免疫信息学工具JanusMatrix，它是经过验证的T细胞表位定位工具EpiMatrix的扩展。本概要中总结的初步探索揭示了所选调节性和效应性T细胞表位与人类基因组、人类微生物组和所选人类病原体中的其他表位在TCR交叉反应方面似乎存在的重要差异。除了探索人类自身、共生体和病原体之间的T细胞表位关系外，JanusMatrix还可能有助于探索异源免疫的某些方面，并检查人类所接触的病原体之间的T细胞表位相关性（例如登革热血清型，或丙型肝炎病毒和流感）。例如，在手足口病（HFMD）中，广泛的肠道病毒和人类微生物组交叉反应（以及与人类基因组有限的交叉反应）似乎预示着免疫优势。相比之下，对于所选的调节性T细胞（Treg）表位，观察到与人类基因组中所含蛋白质的交叉反应比与人类微生物组的更广泛。虽然可能无法预测所有免疫反应的影响，但人类基因组、人类微生物组以及一系列人类病原体和疫苗的序列数据的可用性使得通过计算驱动探索T细胞表位交叉反应的影响成为可能。这是对JanusMatrix的首次描述，它是一种评估TCR交叉反应的算法，可能有助于提供一种预测对所选T细胞表位作出反应的T细胞表型的方法。无论是用于探索T细胞表型，还是用于评估病毒表位的TCR面相关病毒株之间的交叉保守性，进一步的JanusMatrix研究都可能有助于开发更安全、更有效的疫苗。