Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany.
Medical Department I, Universitätsklinikum der Ruhr-Universität Bochum, Ruhr-Universität Bochum, Hölkeskampring 40, Herne, Germany.
Transplantation. 2019 Aug;103(8):1544-1555. doi: 10.1097/TP.0000000000002776.
There is a clear medical need to change the current strategy of "one-size-fits-all" immunosuppression for controlling transplant rejection to precision medicine and targeted immune intervention. As T cells play a key role in both undesired graft rejection and protection, a better understanding of the fate and function of both alloreactive graft-deteriorating T cells and those protecting to infections is required. The T-cell receptor (TCR) is the individual identity card of each T cell clone and can help to follow single specificities. In this context, tracking of lymphocytes with certain specificity in blood and tissue in clinical follow up is of especial importance. After overcoming technical limitations of the past, novel molecular technologies opened new avenues of diagnostics. Using advantages of next generation sequencing, a method was established for T-cell tracing by detection of variable TCR region as identifiers of individual lymphocyte clones. The current review describes principles of laboratory and computational methods of TCR repertoire analysis, and gives an overview on applications for the basic understanding of transplant biology and immune monitoring. The review also delineates methodological pitfalls and challenges. With the outlook on prediction of antigens in immune-mediated processes including those of unknown causative pathogens, monitoring the fate and function of individual T cell clones, and the adoptive transfer of protective effector or regulatory T cells, this review highlights the current and future capability of TCR repertoire analysis.
有一种明确的医学需求，需要将目前控制移植排斥反应的“一刀切”免疫抑制策略转变为精准医学和靶向免疫干预。由于 T 细胞在不期望的移植物排斥和保护中都起着关键作用，因此需要更好地了解同种异体反应性移植物恶化 T 细胞和那些抗感染保护 T 细胞的命运和功能。T 细胞受体 (TCR) 是每个 T 细胞克隆的个体身份证，可以帮助追踪单个特异性。在这种情况下，在临床随访中追踪血液和组织中具有特定特异性的淋巴细胞尤为重要。在克服了过去的技术限制之后，新的分子技术为诊断开辟了新途径。利用下一代测序的优势，建立了一种通过检测可变 TCR 区域作为个体淋巴细胞克隆标识符来追踪 T 细胞的方法。本综述描述了 TCR 库分析的实验室和计算方法的原理，并概述了其在基础理解移植生物学和免疫监测中的应用。该综述还阐述了方法学上的陷阱和挑战。通过预测包括未知病原体引起的免疫介导过程中的抗原，监测个体 T 细胞克隆的命运和功能，以及保护性效应或调节性 T 细胞的过继转移，该综述强调了 TCR 库分析的当前和未来能力。
