美国麻省理工学院和哈佛大学的布罗德研究所Fei Chen和Catherine J. Wu共同合作近期取得重要工作进展，他们通过研究T细胞受体和转录组的空间图谱，揭示了适应性免疫反应中不同的免疫生态位及其相互作用。该项研究成果2022年10月11日在线出版于《免疫》杂志上。

确定组织中T细胞克隆型的空间分布对理解T细胞行为至关重要，但空间测序方法仍然无法对TCR库进行分析。研究人员开发了一种10 μm分辨率的Slide-TCR-seq方法，对完整组织中的整个转录组和TCRs进行测序。研究小组证实了Slide-TCR-seq能够定位小鼠脾脏中T细胞及其受体的特征位置。

在人类淋巴细胞生发中心，他们发现了空间上不同的TCR类型。肾细胞癌和黑色素瘤标本中的T细胞表现出不同的免疫反应:克隆内和克隆间T细胞状态和浸润不同，相邻肿瘤和免疫细胞表现出不同的基因表达。总之，他们的方法对克隆性、邻近细胞类型和驱动T细胞反应的基因表达之间的空间关系有了深入的了解。

据了解，T细胞通过其克隆型T细胞受体（TCRs）的特异性和多样性介导对疾病的抗原特异性免疫反应。

附：英文原文

Title: Spatial maps of T cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response

Author: Sophia Liu, J. Bryan Iorgulescu, Shuqiang Li, Mehdi Borji, Irving A. Barrera-Lopez, Vignesh Shanmugam, Haoxiang Lyu, Julia W. Morriss, Zoe N. Garcia, Evan Murray, David A. Reardon, Charles H. Yoon, David A. Braun, Kenneth J. Livak, Catherine J. Wu, Fei Chen

Issue&Volume: 2022/10/11

Abstract: T cells mediate antigen-specific immune responses to disease through the specificityand diversity of their clonotypic T cell receptors (TCRs). Determining the spatialdistributions of T cell clonotypes in tissues is essential to understanding T cellbehavior, but spatial sequencing methods remain unable to profile the TCR repertoire.Here, we developed Slide-TCR-seq, a 10-μm-resolution method, to sequence whole transcriptomesand TCRs within intact tissues. We confirmed the ability of Slide-TCR-seq to map thecharacteristic locations of T cells and their receptors in mouse spleen. In humanlymphoid germinal centers, we identified spatially distinct TCR repertoires. ProfilingT cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immuneresponses: T cell states and infiltration differed intra- and inter-clonally, andadjacent tumor and immune cells exhibited distinct gene expression. Altogether, ourmethod yields insights into the spatial relationships between clonality, neighboringcell types, and gene expression that drive T cell responses.

DOI: 10.1016/j.immuni.2022.09.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00415-0