生物
T细胞受体
免疫系统
转录组
获得性免疫系统
T细胞
免疫受体
细胞生物学
免疫学
基因
基因表达
遗传学
作者
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
出处
期刊:Immunity
[Elsevier]
日期:2022-10-01
卷期号:55 (10): 1940-1952.e5
被引量:34
标识
DOI:10.1016/j.immuni.2022.09.002
摘要
T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic T cell receptors (TCRs). Determining the spatial distributions of T cell clonotypes in tissues is essential to understanding T cell behavior, 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 transcriptomes and TCRs within intact tissues. We confirmed the ability of Slide-TCR-seq to map the characteristic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we identified spatially distinct TCR repertoires. Profiling T cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immune responses: T cell states and infiltration differed intra- and inter-clonally, and adjacent tumor and immune cells exhibited distinct gene expression. Altogether, our method yields insights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses.
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