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

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-mm-resolution method, to sequence whole tran-scriptomes and TCRs within intact tissues. We confirmed the ability of Slide-TCR-seq to map the character-istic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we iden-tified 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 in-sights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses.