T cell antigen discovery via signaling and antigen-presenting bifunctional receptors
T cell antigen discovery via signaling and antigen-presenting bifunctional receptors
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DOI：
10.1038/s41592-018-0304-8
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发表时间：
2019-02-01
期刊：
影响因子：
48
通讯作者：
Baltimore, David
中科院分区：
文献类型：
--
作者：
Joglekar, Alok, V;Leonard, Michael T.;Baltimore, David
CD8（+）T细胞以抗原特异性方式识别和消除肿瘤。尽管在表征抗肿瘤T细胞库和功能方面取得了进展，但靶抗原的鉴定仍然是一个挑战。在这里，我们描述了称为信号传导和抗原呈递双功能受体（SABR）的嵌合受体在基于细胞的T细胞受体（TCR）抗原发现平台中的应用。SABR呈递包含肽和主要组织相容性复合物（MHC）的细胞外复合物，并在与同源TCR结合后经由TCR样信号诱导细胞内信号传导。我们设计了一种策略，抗原发现使用SABR库筛选数千个抗原表位。我们通过鉴定已知特异性的公共TCR识别的靶标来验证该平台。此外，我们将这种方法扩展到个性化的新抗原发现。
CD8(+) T cells recognize and eliminate tumors in an antigen-specific manner. Despite progress in characterizing the antitumor T cell repertoire and function, the identification of target antigens remains a challenge. Here we describe the use of chimeric receptors called signaling and antigen-presenting bifunctional receptors (SABRs) in a cell-based platform for T cell receptor (TCR) antigen discovery. SABRs present an extracellular complex comprising a peptide and major histocompatibility complex (MHC), and induce intracellular signaling via a TCR-like signal after binding with a cognate TCR. We devised a strategy for antigen discovery using SABR libraries to screen thousands of antigenic epitopes. We validated this platform by identifying the targets recognized by public TCRs of known specificities. Moreover, we extended this approach for personalized neoantigen discovery.