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

• DOI: 10.1016/j.immuni.2022.09.002
• Publication Date: 2022-10-11T15:07:11Z
• Authors: Sophia Liu; J. Bryan Iorgulescu; Shuqiang Li; Mehdi Borji; Irving A. Barrera...; 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
• Keywords: Immune receptor

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.