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Immunity DOI:10.1016/j.immuni.2022.09.002

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

Publication TypeJournal Article
Year of Publication2022
AuthorsLiu, S, J Iorgulescu, B, Li, S, Borji, M, Barrera-Lopez, IA, Shanmugam, V, Lyu, H, Morriss, JW, Garcia, ZN, Murray, E, Reardon, DA, Yoon, CH, Braun, DA, Livak, KJ, Wu, CJ, Chen, F
Date Published2022 Oct 11

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.


Alternate JournalImmunity
PubMed ID36223726