T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes
T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes
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DOI：
10.1016/j.cell.2019.07.009
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发表时间：
2019-08-08
期刊：
影响因子：
64.5
通讯作者：
Elledge, Stephen J.
中科院分区：
文献类型：
--
作者：
Kula, Tomasz;Dezfulian, Mohammad H.;Elledge, Stephen J.
T细胞对特定抗原的识别介导了对病原体的保护和控制肿瘤，但也可以引起自身免疫。我们对T细胞抗原及其对人类健康的影响的了解受到T细胞图谱技术的技术限制。在这里，我们介绍了T-SCAN，一个高通量的识别T细胞识别的抗原的平台。T-SCAN使用慢病毒将抗原库送入细胞，进行内源性处理，并呈现在主要组织相容性复合体(MHC)分子上。使用颗粒酶B活性报告分离T细胞功能识别的靶细胞，并通过下一代测序鉴定介导识别的抗原。我们展示了T-SCAN从病毒和人类基因组文库中正确识别T细胞受体(TCR)的同源抗原。我们应用T-SCAN发现新的病毒抗原，进行TCR特异性的高分辨率映射，并表征肿瘤来源的TCR的反应性。T扫描是研究T细胞反应的一种强有力的方法。
T cell recognition of specific antigens mediates protection from pathogens and controls neoplasias, but can also cause autoimmunity. Our knowledge of T cell antigens and their implications for human health is limited by the technical limitations of T cell profiling technologies. Here, we present T-Scan, a high-throughput platform for identification of antigens productively recognized by T cells. T-Scan uses lentiviral delivery of antigen libraries into cells for endogenous processing and presentation on major histocompatibility complex (MHC) molecules. Target cells functionally recognized by T cells are isolated using a reporter for granzyme B activity, and the antigens mediating recognition are identified by next-generation sequencing. We show T-Scan correctly identifies cognate antigens of T cell receptors (TCRs) from viral and human genome-wide libraries. We apply T-Scan to discover new viral antigens, perform high-resolution mapping of TCR specificity, and characterize the reactivity of a tumor-derived TCR. T-Scan is a powerful approach for studying T cell responses.